The biologic activity of dehydroepiandrosterone sulfate (DHAS) has been studied in 5 hypogonadal males, ages 15–35, and a 3-month-old female with 21 trisomy syndrome. DHAS, 100 mg daily, was administered orally for 27–48 days to the male subjects and 25 mg daily to the infant. Sebum production, measured before and on the final days of DHAS, was used as a measure of androgenic activity. It was low initially and increased significantly during therapy in all but one of the male subjects. Sebum production also increased in the female infant. Serial vaginal smears showed maturation of the vaginal epithelium typical of estrogen effect. Regression to an atrophic state occurred after cessation of therapy. Neither nitrogen retention nor an increase in urinary hydroxyproline excretion was documented in 2 patients maintained on metabolic balance. Plasma concentrations of DHAS and testosterone (T) were low in all hypogonadal males; unconjugated DHA was low in 2 patients. During therapy, DHA and T remained unchanged while DHAS increased 2- to 5-fold in 3 of the 5 patients. This study demonstrates that administration of DHAS may produce androgenic as well as estrogenic effects and is the first evidence for the steroid's biologic potential in man.