Accelerated apoptosis is a significant factor in the pathophysiology of male infertility disorders associated with abnormal spermatogenesis. This study aimed to investigate apoptosis in varicocele-bearing testes. Sixty four men with varicocele (18 fertile and 46 infertile) were studied compared with eight men with obstructive azoospermic as controls. Apoptosis was assessed in testicular biopsy specimens using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) method as well as electron microscopy. The results demonstrated that the occurrence of apoptotic changes comprised all types of germ cells but not affecting Sertoli cells. Mean tubular apoptotic indices of fertile or infertile men with varicocele were significantly higher than controls (mean +/- SD 4.55 +/- 1.03%, 6.29 +/- 1.82% versus 2.71 +/- 0.45%, P < 0.05). Mean Leydig cells apoptotic indices of infertile men with varicocele were significantly higher than those of fertile men without varicocele as well as controls (1.18 +/- 0.38%, 0.68 +/- 0.15%, 0.31 +/- 0.21%, P < 0.05). Apoptotic indices were nonsignificantly correlated with Johnsen score, testicular volume or varicocele grade. It is concluded that testicular apoptosis is increased in varicocele-associated men either fertile or infertile who may be implicated in associated spermatogenic dysfunction.