Forty depressed patients and 36 age- and sex-matched controls were given 250 micrograms ACTH1-24 by IV bolus. Plasma steroid hormone levels were measured prior to and 60 min after ACTH administration. The depressed patients had significantly greater cortisol (F), 11-deoxycortisol (S), androstenedione (AD), and 17 alpha-hydroxyprogesterone (17 alpha-OHP) responses (delta; p less than 0.05) and a marginally greater 11 beta-hydroxyandrostenedione (11 beta-OHAD) response (delta; p = 0.091) than the controls. There was no significant difference in the corticosterone (B) response between the two groups. With the exception of 11 beta-OHAD, all the steroid hormones were significantly negatively correlated with age in the controls, but only S and AD marginally demonstrated this relationship in the depressed patients. F, S, AD, 17 alpha-OHP, and B, but not 11 beta-OHAD, were significantly positively correlated with each other in the controls, but only F was significantly correlated with AD in the depressed patients. These data suggest that the hypercortisolemia found in some depressed patients involves increased precursor and metabolite levels both at baseline and in response to exogenous ACTH, compared to controls. Furthermore, variability in these precursors is greater in depressed patients, and their relationship to age is lost. These findings are consistent with the hypothesis that adrenal products other than cortisol also could be related to affective symptoms.