We evaluated the effects of chronic renal failure (CRF) on testicular function and semen physiology. A CRF model was created in 48 male rats by performance of five-sixths nephrectomies in two-stage procedures, and a control (group A) by two-stage sham operation on six male rats. Seven weeks later, serum urea and creatinine concentrations were assessed, and the nephrectomized rats were then equally divided into four groups, B, C, D and E, and treated with saline, erythropoietin, bromocryptine and hydralazine, respectively. Seventeen weeks after the first surgical procedure, the number of fertile rats, the mean values of epididymal sperm content and motility, the outcome of in vitro fertilization, and peripheral serum testosterone concentrations and responses to human chorionic gonadotropin were significantly higher (P < 0.05) in groups A, C and D than in groups B and E. Serum prolactin concentration was significantly higher (P < 0.05) in all groups of nephrectomized rats than in group A. Our results indicate that bromocryptine and erythropoetin improve Leydig cell function, spermatogenesis epididymal sperm maturation, and sperm fertilizing capacity in rats with CRF.