The genotoxicity of megestrol acetate was studied in mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Megestrol acetate (8.12, 16.25 and 32.50 mg/ kg of body weight) was injected intraperitoneally separately in different groups of animals. Both CAs and SCEs were statistically increased at 16.25 and 32.50 mg/kg of body weight. Our earlier in vitro studies show the generation of free oxygen radicals, by synthetic progestins responsible for the genotoxic damage. As the genotoxic effects of steroids can be reduced by natural products having antioxidant properties, and ascorbic acid possesses antioxidant activity, ascorbic acid (20, 40 or 60 mg/kg of body weight) administered together with megestrol acetate (32.50 mg/kg of body weight) significantly decreased CAs and SCEs, suggesting an antigenotoxic role of ascorbic acid against megestrol acetate-induced genotoxic damage in mice bone marrow cells. The antigenotoxic effect was clearly dose dependent. The highest protective effect was observed at 60 mg/kg body weight of ascorbic acid treated with 32.50 mg/kg body weight of megestrol acetate.