Background: Total sleep deprivation in rodents and in humans has been associated with hyperphagia. Over the past 40 years, self-reported sleep duration in the United States has decreased by almost 2 hours. Objective: To determine whether partial sleep curtailment, an increasingly prevalent behavior, alters appetite regulation. Design: Randomized, 2-period, 2-condition crossover clinical study. Setting: Clinical Research Center, University of Chicago, Chicago, Illinois. Patients: 12 healthy men (mean age [+/-SD, 22 +/- 2 years; mean body mass index [+/-SD], 23.6 +/- 2.0 kg/M-2). Measurements: Daytime profiles of plasma leptin and ghrelin levels and subjective ratings of hunger and appetite. Intervention: 2 days of sleep restriction and 2 days of sleep extension under controlled conditions of caloric intake and physical activity. Results: sleep restriction was associated with average reductions in the anorexigenic hormone leptin (decrease, 18%; P= 0.04), elevations in the orexigenic factor ghrelin (increase, 28%; P < 0.04), and increased hunger (increase, 24%; P < 0.01) and appetite (increase, 23%; P = 0.01), especially for calorie-dense foods with high carbohydrate content (increase, 33% to 45%; P= 0.02). Limitations: The study included only 12 young men and did not measure energy expenditure. Conclusions: Short sleep duration in young, healthy men is associated with decreased leptin levels, increased ghrelin levels, and increased hunger and appetite.