In order to determine the efficacy of gonadotropin and gonadotropin-releasing hormone (GnRH) therapy in hypogonadotropic hypogonadal men, we performed a retrospective clinical analysis in the outpatient clinic of a University Center for Reproductive Medicine, Twenty-six men with either hypothalamic (idiopathic hypogonadotropic hypogonadism, N = 6; Kallmann syndrome, N = 8) or pituitary disorders (N = 12) were treated with gonadotropins or GnRH for induction of spermatogenesis in 33 treatment cycles and, additionally, for induction of pregnancy in the female partner in 18 out of 33 cases (12 of 26 patients). Patients were treated with a combination of 1000-2500 IE of human chorionic gonadotropin twice per week and 75-150 IE human menopausal gonadotropin three times per week intramuscularly or subcutaneously. Alternatively, GnRH was administered at doses of 5-20 micrograms every 120 min subcutaneously to men with hypothalamic disorders. Treatment lasted until sperm appeared in the ejaculate or pregnancy was induced. During therapy, testosterone levels increased into the normal range. Total testicular volumes increased significantly during therapy despite low initial testicular volumes and histories of maldescended testes. Sperm appeared in the ejaculate in 30 of 33 treated patients. Pregnancies occurred in 15 out of 18 cases even with sperm counts far below the normal range. We could not detect differences in the efficacy of gonadotropin or GnRH treatment in hypogonadotropic hypogonadism. Thus, we conclude that both gonadotropin and pulsatile GnRH therapy are most effective in the induction of spermatogenesis and pregnancies in hypogonadotropic hypogonadal men, despite maldescended testes, low initial testicular volumes or sperm concentrations below the normal limit.