Patients who have severe hypogonadotropic hypogonadism caused by presumed hypothalamic disease often have a subnormal LH response to a bolus dose of gonadotropin-releasing hormone (GnRH). To determine if this subnormal response is the result of lack of exposure of the pituitary gonadotroph cells to GnRH, five such men were given daily infusions of 500 microgram GnRH, for 7 days. A standard 250-microgram bolus test dose of GnRH was administered before and again immediately after the week of GnRH infusions. Five men who had severe hypogonadotropic hypogonadism as a result of presumed pituitary disease also received daily GnRH infusions for 1 week. The mean incremental LH responses (+/- SE) to GnRH of the men with presumed hypothalamic disease were 5.0 +/- 1.9 mIU/ml before and 56.9 mIU/ml after the week of infusions. The mean incremental LH responses of the men with presumed pituitary disease were 2.4 +/- 0.7 mIU/ml before and 3.7 +/- 2.9 mIU/ml after the week of infusions. These data suggest that the normal gonadotroph requires prolonged exposure to GnRH for LH responsiveness to become normal, but that the severely damaged gonadotroph cannot be stimulated to release LH normally even by the same prolonged stimulation with GnRH.