One hundred nineteen euprolactinemic anovulatory infertility patients who were being evaluated for induction of ovulation with clomiphene citrate were studied to determine the prevalence of increased adrenal androgen (AA) secretion in this group. Fifty percent of these patients exhibited increased AA secretion, as evidenced by an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level. Seventy-seven percent of these women with elevated levels of DHEA-S were nonhirsute . Twenty-six patients with elevated serum DHEA-S levels underwent adrenocorticotropic hormone (ACTH) stimulation tests in order to determine a possible mechanism(s) for the increase in DHEA-S. Plasma ACTH, as well as total, low-density lipoprotein, and high-density lipoprotein cholesterol were also measured. These levels were normal and did not correlate with the elevated levels of DHEA-S. Seven of 16 patients (34%) had exaggerated responses of serum DHEA-S and of 17-OH pregnenolone to ACTH stimulation. In six of these seven patients, our data suggested the occurrence of a mild deficiency of 3 beta-ol dehydrogenase-isomerase. All of these six patients were considered to have polycystic ovary syndrome. While these data do not explain the increased AA secretion in the majority of patients with elevated levels of DHEA-S, we suggest that serum DHEA-S is frequently elevated in anovulatory infertile patients.