The hormone dehydroepiandrosterone (DHEA) has been reported to have beneficial effects on obesity, diabetes mellitus, and serum lipids in animal studies, but results in human studies are less clear. We conducted a randomized double-blind placebo-controlled trial to determine the effects of DHEA treatment on obesity and related physiologic conditions in adolescents and young adults. In this 10-week study, 13 morbidly obese subjects received a placebo for 2 weeks. After this run-in period, patients were randomized, with seven subjects (mean age, 15.5 years; body mass index [BMI, derived by dividing body weight in kilograms by height in meters squared], 48.2 +/- 9.7 [mean +/- SD]) receiving DHEA 40 mg sublingually twice daily for 8 weeks and six subjects (mean age, 18.0 years; BMI, 52.9 +/- 14) receiving placebo. Variables measured included body weight, body composition, resting metabolic rate (RMR), serum lipid levels, insulin sensitivity, and serum steroid levels. Treatment with DHEA resulted in a statistically significant increase in plasma DHEA and DHEA sulfate (DHEAS) concentrations (P < .01). Testosterone (T) levels were significantly increased in females who received DHEA. DHEA administration had no effect on body weight, sense of well-being, or any other measured variables. These findings suggest that DHEA 40 mg administered sublingually twice daily for 8 weeks has no positive effect on body weight, body composition, serum lipids, or insulin sensitivity in extremely obese adolescents and young adults.