The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p < 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.