Effect of oral administration (25 and 100 mg/kg body wt/day, for 20 and 90 days) of fruit powder of Piper nigrum L. on the male reproductive organs of mice, Parkes strain, was investigated. Various reproductive end points such as organs weight, histopathology, sperm parameters, sialic acid and fructose contents, and fertility indices were assessed. Histologically, testes in treated mice, except in those treated with 100 mg of dose for 90 days, showed non-uniform degenerative changes in the seminiferous tubules, as both affected and normal tubules were observed in the same section. In mice treated with 100 mg dose for 90 days, degenerative changes were observed in all the tubules. Affected seminiferous tubules showed intraepithelial vacuolation, loosening of germinal epithelium, occurrence of giant cells, and mixing of spermatids of different stages of spermatogenesis; in severe cases, the tubules were lined by mainly a layer of Sertoli cells. Percentage of affected tubules in testes of Piper-treated mice was dose-and duration-related. Further, Piper nigrum treatment for 20 days did not cause appreciable alterations in histological appearance of the epididymis, while the treatment for 90 days caused detectable alterations in the duct. The treatment also had adverse effects on sperm parameters, levels of sialic acid and fructose, and on litter size. Fifty six days after cessation of treatment, the alterations induced in the reproductive organs recovered to control levels, though the litter size in females impregnated by Piper-treated males remained significantly decreased compared to controls.