Men with acquired hypogonadotropic hypogonadism treated with testosterone are generally assumed to be infertile. The finding of two such patients with unexpected fertility and normal sperm counts prompted an evaluation of spermatogenesis in additional men with this condition. Case records were initially searched and one similar case with fertility was found. Subsequently, 12 consecutive men with acquired hypogonadotropic hypogonadism were evaluated for gonadal function and sperm production while receiving testosterone. In five of the cases with proven spermatogenesis, exon 10 of the FSH receptor was sequenced to look for activating mutations. The original three cases and four of the subsequent 12 men had sperm concentrations > or = 15 million/ml. Two additional men had concentrations of 1 million/ml and six were azoospermic. Residual LH and FSH levels were slightly higher in those with maintained spermatogenesis prior to testosterone replacement. No activating mutations were found in exon 10 of the FSH receptor in the five cases studied. We conclude that men with acquired hypogonadotropic hypogonadism being treated with testosterone should not be assumed to be sterile, as we have found that more than half have been shown to have persistent spermatogenesis with more than one-third having sperm concentrations > or = 15 million/ml. This may be related to fact that gonadotropin levels in such patients are present, albeit low. Semen analyses in such men should be routinely carried out so that they can be appropriately counseled regarding potential fertility.