Serum dehydroepiandrosterone sulfate (DHEA-S) is frequently elevated in anovulatory women. This study was carried out to determine whether the ovulatory response with clomiphene citrate (CC) in patients with elevated levels of serum DHEA-S is influenced by the pretreatment level. Also evaluated was whether this response rate was similar to or different from that of anovulatory patients who had normal levels of DHEA-S. CC was administered to 40 anovulatory patients who had elevated levels of DHEA-S. Rankit analysis of these 40 elevated DHEA-S levels indicated that two populations existed. These patients were, therefore, divided into two groups of 29 and 11 with DHEA-S levels of less than 5 and greater than 5 micrograms/ml, respectively. Fifty-nine anovulatory patients with normal DHEA-S levels were also treated with CC. Patients with elevated and normal DHEA-S levels had similar rates of ovulation with CC (75% and 78%). Among patients with elevated levels of DHEA-S, ovulation occurred in 55% of patients with levels greater than 5 micrograms/ml and 83% with levels less than 5 micrograms/ml. The dose of CC at which ovulation occurred was unrelated to the level of DHEA-S. Pregnancies occurred in 15 of the 40 patients after at least four ovulatory cycles and were not influenced by the level of DHEA-S. It is concluded that CC is effective in inducing ovulation in patients with elevated levels of adrenal androgens. However, in patients with DHEA-S levels greater than 5 micrograms/ml, the ovulatory response rate may be decreased.