We have studied the effects of administration of dexamethasone, 2 mg orally every 6 hours, for 5 days on the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) induced by luteinizing hormone-releasing hormone (LHRH) in six women with secondary amenorrhea and on the release of these gonadotropins induced by clomiphene citrate in 10 women with secondary amenorrhea. Dexamethasone suppressed baseline serum levels of LH and FSH and blunted the LHRH-induced release of LH and FSH in six women. Following dexamethasone administration, the LH and FSH response to clomiphene citrate, which competes for gonadal steroid receptor binding sites in the hypothalamus, resulting in increased release of LHRH, was blunted in the 10 women studied. The data indicate that short-term administration of pharmacologic doses of glucocorticoids suppresses the secretion of LH and FSH by a direct effect on the anterior pituitary and possibly by an effect at the suprahypophyseal level with inhibition of release of LHRH.