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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.
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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.
Each chapter follows a domain of the published exam outline. Practise one on its own:
A sample of 12 multiple-choice questions from the bank, with the full rationale shown.
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?
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:
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.
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?
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?
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.
Which neurotransmitter abnormality is most strongly implicated in major depressive disorder and is the target of SSRIs?
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.
Which muscle fiber type is fatigue-resistant, has high mitochondrial content, and relies primarily on oxidative metabolism?
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.
On the cardiac action potential of a ventricular myocyte, what causes the plateau (phase 2)?
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).
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:
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.
Where is intrinsic factor produced?
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.
Where in the nephron is most filtered glucose normally reabsorbed?
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.
BRCA1/2 mutations significantly increase lifetime risk of:
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.
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?
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.
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.
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 →
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.
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.
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.
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.
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.
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.