Numerous reports have shown that serotonin (5-HT) has a detrimental effect on spermatogenesis and androgen synthesis. Serotonin has two mechanisms of action on the testicle: (1) vasoconstrictive changes possibly causing premature sloughing of spermatozoa, and (2) alteration of androgen metabolism. The data in our animals with the experimental varicocele clearly mimic the human situation. All seminal parameters except volume are decreased after the varicocele is created. In many infertile patients with a varicocele, serotonin may be the inciting factor which results in subfertile semen. This is corroborated by the presence of elevated serotonin levels in spermatic vein plasma of most patients with a varicocele who undergo surgery. More data, comparing the relationship between spermatic vein and peripheral blood serotonin levels in patients with and without a varicocele, are needed. This investigation is being pursued in patients undergoing inguinal surgery for other lesions.