Basal and ACTH-stimulated plasma levels of cortisol, delta 4-androstenedione, and dehydroepiandrosterone (DHEA) were measured in a group of 11 female patients with postadolescent acne resistant to or relapsing after conventional therapy and in a group of 10 normal women without acne or hirsutism. Each patient received, in a blinded random fashion, a series of 5 1-h ACTH tests. For each test a different dose of ACTH-(1-24) was administered, ranging from 0-1 microgram/kg, given as an iv bolus. Blood samples were collected 0, 10, 30, and 60 min after ACTH bolus injection. Patients with acne had slightly higher concentrations of basal cortisol, delta 4-androstenedione, and DHEA than normal controls (P less than 0.05). After ACTH-(1-24) stimulation, the same patients had greater peak and time-integrated DHEA concentrations (P less than 0.03). The ED50 values of the cortisol dose-response curves were similar in patients and normal women (P less than 0.05), suggesting that there are no differences in the sensitivity of the adrenal cortex to ACTH between the acne patients and the controls studied. The ratio of DHEA to cortisol response was significantly elevated in women with acne compared to that in control women, suggesting some preponderance of the delta 5 pathway of steroidogenesis in acne (P less than 0.05). These findings of basal and ACTH-stimulated hypersecretion of delta 5-androgens in patients with postaldolescent acne are consistent with an increased volume of androgen-secreting tissue, rather than hypersensitivity of the adrenal zona reticularis to ACTH.