Infertile men with varicocele or idiopathic infertility were compared with a control group. Spermocytograms were taken and the following radioimmunological plasma analyses carried out: testosterone, FSH and LH before and after 50 micrograms LRH, Prolactin (PRL) before and after 200 micrograms TRH; in addition, 8 patients with varicoceles and 3 controls received LRH intravenously (0.4 microgram/min.) for 4 hours. The binding of [125I] human chorionic gonadotrophin (hCG) to testicular tissue obtained by biopsy from 10 infertile men was also investigated. Of the parameters studied, no differences were found between the unilateral or bilateral varicoceles. In the two groups of infertile men, sperm motility and percentage normal forms were similar and significantly lower than in controls. As compared to the controls, in the groups of infertile men, basal LH and testosterone levels were no different but basal FSH levels was increased, basal PRL was higher (p less than 0.05) in the varicocele group. Responses of the LH, FSH and PRL to LRH and TRH stimulations were generally higher in infertile men than in controls. As compared to the idiopathic infertile men, testosterone levels and responses of plasma FSH to LRH injection were lower in varicocele group. Moreover, in infertile men with varicocele, age was correlated negatively with sperm motility and testosterone level and it was correlated positively with LH response to LRH injection. For each patient, testicular tissue was able to specifically bind [125I]hCG, but in some cases of varicoceles, hCG binding capacity was different in the two testes and seemed higher than that observed in men with obstructive azoospermia. These results suggest: 1) dysfunction in both spermatogenesis and Leydig cells with a compensatory hyperfunction of the pituitary gland in infertile men with varicocele; 2) worsening in Leydig cells and tubular lesions with longer duration of varicocele; and 3) absence of any gross abnormality in hCG binding to its specific receptors in the testis of men with varicocele. These data suggest varicoceles may play a causal role in infertility.