Abstract: A preliminary study to evaluate if long term treatment of Methanol Sub-Fraction (MSF) of the seeds of Carica papaya as a male contraceptive would develop neoplastic lesions in vital organs was carried out in albino rats at 50, 250 and 500 mg kg-1 b.wt. day-1 for a period of 24 months, with a minimum dose being one therapeutic dose. Pre-terminal deaths, 45% in males and 48% in females, well within the acceptance limit, were reported to be age related and not treatment related, resulted due to general/respiratory/gastrointestinal/ urogenital disorders in both males and females of control and treated animals. Skin peeling, withering of fur leaving skin patches were observed in few of the animals after 18 months of treatment. Absence of spermatozoa in the cauda epididymis was evident in all the treated animals. No major structural changes compared to control were evident in the vital organs. Serum testosterone, serum electrolytes, tissue biochemical, hematology and clinical chemistry were comparable to those of control animals, suggesting no adverse effect of the test substance following long term treatment. The results provided evidence that the methanol sub-fraction of the seeds of Carica papaya does not lead any development of neoplastic lesion following life term treatment for 24 months in rats and is safe enough to be permitted for further trials as a male contraceptive.