The effect of clomiphene (100 mg daily for 10 days) and ethinyl oestradiol (100 mug daily for 10 days) on the gonadotrophin response to synthetic LHRH has been investigated in two groups of five normal males. A third group of five men served as control group. LHRH, 25 mug, was injected intravenously on days 0, 4, 7 and 10 and the response of serum LH and FSH was monitored by radioimmunoassay. In contrast to the wide inter-individual variation of the response pattern, the intra-individual variation of the response to LHRH in the control group was small. Clomiphene induced a significant elevation of the baseline levels of LH and FSH after a few days of treatment; the pituitary responsiveness to LHRH, however, was significantly reduced. Oestrogen treatment resulted in a uniform suppression of both basal gonadotrophin levels and pituitary responsiveness. The decreased gonadotrophin response to LHRH during clomiphene treatment is thought to be caused by a relative and temporary pituitary depletion of the releasable gonadotrophin content. Although the suppression of LH and FSH response during oestrogen treatment may point to a direct inhibitory effect of oestrogen on pituitary gonadotrophin release, an indirect hypothalamic pathway, through suppression of endogenous LHRH, cannot be ruled out.