Seminiferous epithelium histology, Leydig cell density, and in vitro testosterone synthesis were quantitated in bilateral testicular biopsies from men with varying degrees of unilateral or bilateral varicoceles. Results were correlated with plasma levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone (T), as well as with semen quality. In patients with bilateral varicoceles, spermatogenesis, Leydig cell density, plasma T levels, and in vitro T synthesis were significantly lower than in patients with unilateral varicoceles. Varicoceles appeared to affect maximally the latest stages of spermatogenesis. A negative correlation between FSH and LH levels and spermatogenesis was observed; however, a dissociation between the two gonadotropins occurred when spermatogenesis declined. Plasma T levels were within the normal range in all patients. The T:LH ratio was significantly correlated with spermatogenesis and sperm motility. Leydig cell density was abnormally low in oligospermic patients, and it was significantly correlated with in vitro T synthesis, spermatogenesis, sperm motility, and semen volume. Sperm count and motility were significantly correlated in this group of patients, suggesting a common pathophysiology for the effect of varicocele on spermatogenesis and sperm motility. This common pathophysiology appears to be disturbed Leydig cell function resulting in decreased testicular androgen production, in turn causing inadequate spermatogenesis and epididymal function.