The hypothalamic-pituitary-testicular axis and the regulation of prolactin secretion were investigated in eleven male renal transplant recipients. Mean serum levels of testosterone and estrone were normal, whereas those of androstenedione and estradiol were low. Mean basal luteinizing hormone (LH) levels were slightly elevated, but the peak responses to 50 micrograms i.v. gonadotropin-releasing hormone (GnRH) were not dissimilar from controls. Both basal and GnRH-stimulated follicle-stimulating hormone (FSH) levels were elevated (p less than 0.02-0.05) and also positively correlated with the time spent on hemodialysis (p less than 0.005-0.002). Basal prolactin (PRL) levels were normal, in all subjects. Nine out of 11 patients had a normal PRL response to Thyrotropin-releasing Hormone (TRH). However only six out of 11 had a normal response to 200 mg i.v. Cimetidine (Cim). Three subjects normally responding to TRH failed to respond to Cim. Uremic primary hypogonadism is not fully reversed by renal transplantation: a slight defect in the pituitary LH release may persist and the impairment of the tubular testicular function is left unchanged. While uremic hyperprolactinemia is corrected, the responsiveness to PRL-stimulating agents, particularly Cim, is not restored to normal, reflecting a derangement at the pituitary as well as the hypothalamic level.