An alternate approach to vasectomy for long term male contraception following a single intra-vas.application of a traditional plant (Azadirachta indica) product having immunomodulatory properties is described. The intra-vas administration of neem oil to male rats resulted in a block of spermatogenesis without affecting the testosterone production; the seminiferous tubules, although reduced in diameter, appeared normal and contained mostly early spermatogenic cells. No antisperm antibody could be detected in the serum. Unilateral administration of neem oil in the vas resulted in a significant reduction of testicular size and spermatogenic block only on the side of application; the draining lymph node cells of the treated side also showed enhanced proliferative response to in vitro mitogen challenge. These results indicate that intra-vas application of neem oil is effective in blocking fertility in male mammals after a single injection.