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USMLE Step 1 — Medical Licensing practice questions and exam guide

172 multiple-choice questions and 124 flashcards, organised into 10 chapters, written to the USMLE Step 1 Content Description blueprint. Every question carries a full rationale.

Written and maintained by Nick Burton · last updated 2026-08-22 · how we write and review questions

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About the USMLE Step 1 — Medical Licensing exam

USMLE Step 1 Content Description (NBME/FSMB, public) — organized by General Principles + 9 organ-system blocks

CoStudy's USMLE Step 1 — Medical Licensing bank holds 296 items organised into 10 chapters that follow the published blueprint. Every multiple-choice question carries a written rationale explaining why the correct answer is correct and why each distractor is tempting but wrong.

What the USMLE Step 1 bank covers

Each chapter follows a domain of the published exam outline. Practise one on its own:

Free USMLE Step 1 — Medical Licensing practice questions

A sample of 12 multiple-choice questions from the bank, with the full rationale shown.

General Principles of Foundational Science

A 2-year-old child has developmental delay, fair skin, blond hair, blue eyes, and a musty body odor. Newborn screening was not performed. Which enzyme deficiency is MOST likely responsible?

  1. Homogentisate oxidase
  2. Branched-chain alpha-ketoacid dehydrogenase
  3. Phenylalanine hydroxylase
  4. Tyrosinase
  5. Cystathionine beta-synthase

Answer: C — Phenylalanine hydroxylase

C) Correct: phenylketonuria (PKU) — phenylalanine hydroxylase deficiency causes phenylalanine accumulation. Tyrosine becomes essential (hypopigmentation), and phenyl ketones in urine cause musty odor. A) Homogentisate oxidase deficiency = alkaptonuria (dark urine on standing, ochronosis). B) BCKAD deficiency = maple syrup urine disease (sweet odor, not musty) — off-by-one urine-odor trap. D) Tyrosinase deficiency = albinism (hypopigmentation only, no developmental delay or musty odor). E) Cystathionine β-synthase = homocystinuria (Marfanoid habitus, downward lens dislocation, thromboses).

Down syndrome (trisomy 21) features commonly include:

  1. Tall stature with no intellectual changes
  2. No cardiac issues
  3. Distinctive facial features, hypotonia, intellectual disability, increased risk of congenital heart disease (e.g., AV septal defects), early-onset Alzheimer-like changes, and increased leukemia risk
  4. Resistance to all infections

Answer: C — Distinctive facial features, hypotonia, intellectual disability, increased risk of congenital heart disease (e.g., AV septal defects), early-onset Alzheimer-like changes, and increased leukemia risk

C) Standard features. A/B/D) Each contradicts.

Blood & Lymphoreticular / Immune Systems

A 6-year-old African American boy presents with severe bilateral hand and foot pain. Hgb 7, MCV 85, reticulocytes 8%. Peripheral smear shows sickled erythrocytes. Which is the MOLECULAR basis of this disorder?

  1. Deletion of an alpha-globin gene
  2. G6PD enzyme deficiency
  3. Glutamic acid replaced by lysine at position 6 of the beta-globin chain
  4. Defective spectrin causing membrane fragility
  5. Glutamic acid replaced by valine at position 6 of the beta-globin chain

Answer: E — Glutamic acid replaced by valine at position 6 of the beta-globin chain

E) Correct: sickle cell disease (HbS) — point mutation substitutes valine (hydrophobic) for glutamic acid at β6, allowing polymerization of deoxyHbS. A) Alpha-globin gene deletion = α-thalassemia (microcytic, not sickling). C) Glu→Lys at β6 = HbC disease (milder, target cells, not sickling) — off-by-one Hb variant trap. D) Defective spectrin = hereditary spherocytosis (Coombs-negative, no sickling). B) G6PD deficiency causes oxidative hemolysis with bite cells/Heinz bodies, not sickling.

A 28-year-old man presents with painless cervical lymphadenopathy and night sweats. Biopsy shows large binucleate cells with prominent owl-eye nucleoli within a mixed inflammatory background. Which lymphoma subtype has the BEST prognosis?

  1. Lymphocyte-depleted
  2. Mixed cellularity
  3. Nodular sclerosis
  4. Lymphocyte-rich
  5. Nodular lymphocyte-predominant

Answer: D — Lymphocyte-rich

D) Correct: of the classical Hodgkin lymphoma subtypes, lymphocyte-rich has the BEST prognosis (best survival, most reactive lymphocytes, fewest Reed-Sternberg cells). A) Lymphocyte-depleted has the WORST prognosis — direction reversal trap. B) Mixed cellularity has intermediate prognosis. C) Nodular sclerosis is the MOST COMMON subtype (young women, mediastinal mass) — common misconception that 'most common' = 'best prognosis'. E) NLPHL is a separate entity (not classical HL); it has indolent course but the question asks about classical HL subtypes.

Behavioral Health & Nervous Systems/Special Senses

Which neurotransmitter abnormality is most strongly implicated in major depressive disorder and is the target of SSRIs?

  1. Dopamine
  2. Glutamate
  3. Serotonin
  4. Histamine

Answer: C — Serotonin

Monoamine hypothesis: depression involves reduced serotonergic (and noradrenergic) signaling. SSRIs (sertraline, fluoxetine, escitalopram, etc.) block the serotonin reuptake transporter (SERT), increasing synaptic serotonin. Dopamine (A) is more relevant to psychosis and motivation; glutamate (B) is the target of ketamine.

Musculoskeletal, Skin & Subcutaneous Tissue

Which muscle fiber type is fatigue-resistant, has high mitochondrial content, and relies primarily on oxidative metabolism?

  1. Type I (slow oxidative)
  2. Type IIa (fast oxidative-glycolytic)
  3. Type IIx/IIb (fast glycolytic)
  4. All fiber types are equally oxidative

Answer: A — Type I (slow oxidative)

Type I fibers are slow-twitch, red (myoglobin-rich), packed with mitochondria, fatigue-resistant — adapted for endurance. Type IIx/IIb fibers are fast-twitch, white, glycolytic, and fatigue rapidly — adapted for short, explosive efforts.

Cardiovascular System

On the cardiac action potential of a ventricular myocyte, what causes the plateau (phase 2)?

  1. Sodium influx
  2. Potassium efflux only
  3. Balanced calcium influx and potassium efflux
  4. Chloride influx

Answer: C — Balanced calcium influx and potassium efflux

Phase 2 plateau results from a balance between inward Ca²⁺ current through L-type channels and outward K⁺ current. This sustained depolarization is what couples electrical activity to contraction (Ca²⁺-induced Ca²⁺ release from the SR).

Respiratory System

A 35-year-old African American woman presents with cough, dyspnea, and erythema nodosum. CXR shows bilateral hilar lymphadenopathy. Biopsy of a lymph node would MOST likely show:

  1. Caseating granulomas with acid-fast bacilli
  2. Eosinophilic infiltrate with Curschmann spirals
  3. Reed-Sternberg cells
  4. Anthracotic pigment-laden macrophages
  5. Noncaseating granulomas with multinucleated giant cells

Answer: E — Noncaseating granulomas with multinucleated giant cells

E) Correct: sarcoidosis classically presents with bilateral hilar lymphadenopathy + noncaseating granulomas; Löfgren syndrome adds erythema nodosum + arthralgias. A) Caseating granulomas + AFB = tuberculosis — common misconception trap; sarcoid granulomas are NONcaseating. C) Reed-Sternberg cells = Hodgkin lymphoma (can also cause mediastinal LAD but different demographics and no EN). D) Anthracosis is incidental pigment, not a granulomatous disease. B) Curschmann spirals are seen in asthma sputum.

Gastrointestinal System

Where is intrinsic factor produced?

  1. Chief cells of the stomach
  2. Pancreatic acinar cells
  3. G cells of the antrum
  4. Parietal cells of the stomach

Answer: D — Parietal cells of the stomach

Parietal cells produce both gastric acid (HCl) AND intrinsic factor. IF binds vitamin B12 in the duodenum, enabling absorption in the terminal ileum. Pernicious anemia = autoimmune destruction of parietal cells → B12 deficiency.

Renal & Urinary Systems

Where in the nephron is most filtered glucose normally reabsorbed?

  1. Proximal convoluted tubule (PCT)
  2. Thin descending limb of loop of Henle
  3. Distal convoluted tubule
  4. Collecting duct

Answer: A — Proximal convoluted tubule (PCT)

The PCT reabsorbs ~100% of filtered glucose via SGLT2 (apical) and GLUT2 (basolateral). When plasma glucose exceeds ~180 mg/dL, the transporters saturate and glucose appears in urine (glycosuria) — the basis of SGLT2 inhibitor pharmacology.

Reproductive System & Endocrine System

BRCA1/2 mutations significantly increase lifetime risk of:

  1. Lung cancer only
  2. Breast and ovarian cancer (BRCA1 > BRCA2 for ovarian; both elevate breast)
  3. Pancreatic cancer only
  4. Skin cancer only

Answer: B — Breast and ovarian cancer (BRCA1 > BRCA2 for ovarian; both elevate breast)

BRCA1/2 are tumor suppressors involved in homologous-recombination DNA repair. Pathogenic mutations confer high breast-cancer risk; BRCA1 has higher ovarian-cancer risk than BRCA2.

Multisystem Processes & Disorders

A 70-year-old man is admitted with pneumonia. Two days later he develops fever 39.5°C, heart rate 125/min, respiratory rate 26/min, and blood pressure 78/45 mmHg despite 30 mL/kg IV fluid resuscitation. Serum lactate is 4.5 mmol/L. Which term MOST precisely describes his current condition?

  1. Systemic inflammatory response syndrome (SIRS)
  2. Sepsis
  3. Septic shock (sepsis with persistent hypotension requiring vasopressors and elevated lactate despite adequate fluid resuscitation)
  4. Bacteremia
  5. Multi-organ dysfunction syndrome without shock

Answer: C — Septic shock (sepsis with persistent hypotension requiring vasopressors and elevated lactate despite adequate fluid resuscitation)

C) Correct: persistent hypotension (requiring vasopressor support to maintain MAP ≥65) and serum lactate >2 mmol/L DESPITE adequate fluid resuscitation defines septic shock per Sepsis-3 criteria — the most severe, precisely applicable term here given fluid-refractory hypotension and hyperlactatemia. B) 'Sepsis' (life-threatening organ dysfunction from dysregulated host response to infection, e.g., SOFA score increase ≥2) is present but is a less precise/complete answer once fluid-refractory hypotension with hyperlactatemia has developed — this patient has progressed beyond sepsis to septic shock, a half-right trap of choosing an earlier, still-true stage. A) SIRS criteria (temperature, heart rate, respiratory rate, WBC) are nonspecific and no longer the primary diagnostic framework in Sepsis-3; this vignette clearly exceeds SIRS with organ dysfunction and shock. D) Bacteremia refers only to viable bacteria in blood, not the clinical syndrome described. E) The patient DOES have shock (persistent hypotension), so this option is factually incorrect.

USMLE Step 1 — Medical Licensing flashcards

6 sample cards from the 124 in the bank.

Sarcoidosis?

Non-caseating granulomas, bilateral hilar lymphadenopathy, ↑ ACE, hypercalcemia.

Pseudomonas aeruginosa hallmarks?

Gram-negative, oxidase-positive, blue-green pigment, fruity grape smell.

ACE inhibitor side effects?

Cough (bradykinin), angioedema, hyperkalemia, teratogenic.

Pre-renal vs intrinsic AKI?

Pre-renal: BUN/Cr >20, FENa <1%. Intrinsic: BUN/Cr <15, FENa >2%.

Melanoma ABCDE?

Asymmetry, Border irregular, Color variation, Diameter >6mm, Evolving.

MHC class I vs II?

MHC I: all nucleated cells, presents to CD8 T cells. MHC II: APCs only, presents to CD4 T cells.

Practise the full USMLE Step 1 — Medical Licensing bank

These samples are a small slice. The full bank runs flashcards, multiple choice and timed mock exams with per-chapter progress tracking, on the web and in the iOS app.

Open USMLE Step 1 — Medical Licensing →

USMLE Step 1 — frequently asked

How many USMLE Step 1 practice questions does CoStudy have?

The USMLE Step 1 — Medical Licensing bank holds 296 items: 172 multiple-choice questions, 124 flashcards. 18 of them are on this page to read free, with no signup.

Do the USMLE Step 1 questions come with explanations?

Yes. Every multiple-choice item carries a written rationale that states the controlling principle behind the correct answer and then addresses each wrong option in turn — why it tempts and precisely where it fails. Knowing why the plausible answer was wrong is worth more than knowing which letter was right.

What topics does the USMLE Step 1 bank cover?

It is organised into 10 chapters that follow the published exam blueprint: General Principles of Foundational Science; Blood & Lymphoreticular / Immune Systems; Behavioral Health & Nervous Systems/Special Senses; Musculoskeletal, Skin & Subcutaneous Tissue; Cardiovascular System; Respiratory System; Gastrointestinal System; Renal & Urinary Systems; Reproductive System & Endocrine System; Multisystem Processes & Disorders. The number of questions in each chapter is proportional to that domain's published weight, so working through the bank exposes you to roughly the mix the real exam uses.

Are the USMLE Step 1 practice questions free?

The samples on this page are free to read in full, rationales included, with no account. The complete 296-item bank, the timed mock exams and per-chapter progress tracking are part of CoStudy on the web and in the iOS app.

How current is the USMLE Step 1 content?

Last reviewed 2026-08-22. Banks are written against the certifying body's published exam outline and re-checked when that outline changes — exams get renumbered, retired and reweighted, and a bank written to a superseded outline teaches the wrong proportions. Figures that are re-indexed annually are deliberately not asserted as rules; the questions test the governing principle instead.

Primary source

This bank is written against the USMLE program's published exam material. Check the USMLE content outlines for the current outline, fees and eligibility rules — those change, and the certifying body is the only authority on them. CoStudy is not affiliated with the USMLE program.

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