Although testosterone (T) therapy is sufficient for maturation and maintenance of secondary sex characteristics in hypogonadal men, gonadotropins are required for stimulation of spermatogenesis. Thirteen men with hypogonadotropic hypogonadism received treatment with hCG, followed in 12 by the addition of human menopausal gonadotropin (hMG). All initially had undetectable serum LH and FSH and low T levels and were azoospermic with small testes. During therapy, all achieved normal male levels of T. Twelve of 13 had marked and continuous increase in testicular volume. Three men had sperm in the ejaculate with hCG treatment alone. All but 1 patient developed sperm in their seminal fluid during combined hCG and hMG therapy. Two men achieved three pregnancies, and 2 more had semen that produced hamster oocyte penetration assays in the fertile range during the protocol period. Four of 5 who achieved sperm densities greater than 1 million/ml while receiving combined therapy maintained or increased sperm production while receiving continued hCG therapy after hMG was withdrawn. We examined the response to gonadotropin therapy of men who had received previous T therapy and those who had not. There were no differences in rapidity or degree of response, as assessed by rise in serum T, increase in testis volume, or maximal sperm density achieved. Multiple pituitary deficits and cryptorchidism were negative prognostic factors. In summary, the prognosis for successful stimulation of spermatogenesis in men with hypogonadotropic hypogonadism treated with hCG/hMG is good and not adversely affected by prior androgen treatment. Despite undetectable serum FSH levels, hCG treatment was sufficient to both initiate and maintain spermatogenesis in some patients.