The serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the repetitive administration of synthetic gonadotropin-releasing hormone (GnRH) were studied in six male patients with idiopathic hypogonadotropic hypogonadism. Each patient received 50 mug of GnRH intravenously every four hours for 43 consecutive doses, i.e., for one week. Five of the six patients had substantially greater maximum serum LH concentrations in response to the 43rd dose than to the first dose. The mean (+/- SE) maximum serum LH concentration of all six patients following the 43rd dose (14.6 +/- 3.0 mIU/ml) was significantly (P less than 0.01) greater than that to the first dose (8.3 +/- 2.6 mIU/ml. These results suggest that the LH response of the human gonadotroph to GnRH depends on the prior exposure of the gonadotroph to GnRH. All six patients had substantially higher basal serum FSH levels prior to the 43rd dose (13.6 +/- 2.6 mIU/ml) than prior to the first dose (2.8 +/- 0.4; P less than 0.01). Four patients had increases in basal FSH level to within the normal adult male range (5-15 mIU/ml), and two had increases to above it. This uniform elevation of the serum FSH level to normal or above normal suggests that GnRH may be the primary FSH-releasing hormone as well as the primary LH-releasing hormone.