The purpose of the present study was to investigate the antifertility efficacy of Coccinia indica and its possible mechanisms of action on testicular functions in Parkes male mice. Mice were orally administered 50% ethanolic leaf extract of Coccinia indica (200 and 500mgkg−1 body weight day−1) or distilled water (controls) for 35days. To assess reversibility, additional mice were treated with 500mgkg−1 body weight of Coccinia or distilled water for 35days and sacrificed 56days later. Several male reproductive parameters such as motility, viability, morphology and number of spermatozoa in the cauda epididymidis, histopathology, serum level of testosterone, and fertility indices were evaluated; further, activities of 3β- and 17β-hydroxysteroid dehydrogenases, western blot analyses of StAR protein, cytochrome P450scc enzyme and of caspase-3, germ cell apoptosis by TUNEL, and lipid peroxidation and antioxidant enzymes activities in the testis were assessed. Toxicological parameters were also examined. Histologically, testes in Coccinia-treated mice showed nonuniform diverse degenerative changes in the seminiferous tubules. Treatment had adverse effect on serum level of testosterone, steroidogenic markers in the testis and on sperm parameters in the cauda epididymidis. The treatment also affected oxidative status of the testis and induced germ cell apoptosis. Serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were, however, not affected in treated mice. Fertility of the extract-treated males was also suppressed, but their libido remained unaffected. By 56days of treatment withdrawal, the above parameters recovered to control levels, suggesting that the Coccinia treatment causes reversible suppression of spermatogenesis and fertility in P mice, without producing detectable signs of toxicity. Further, suppression of spermatogenesis may be caused by germ cell apoptosis resulting from deficiency of testosterone, which, in turn, may result from the adverse effect of C. indica treatment on steroidogenesis and oxidative status in the testis.