The anticarcinogenic effect of aqueous extract of fruit of Momordica charantia (bitter gourd), which is widely used as a vegetable in India, was studied in a two-step skin carcinogenesis model in mice. The possible mode of action was also investigated. Oral administration of the fruit extract was found to have an adverse effect on the general health and lifespan of the animals when used at a high concentration. But when this dose was reduced by half, the test extract afforded protection from the development of skin tumour and increased life expectancy. Carcinogen-induced lipid peroxidation in liver and DNA damage in lymphocytes were found to be reduced following treatment with Momordica. The fruit extract was found to significantly activate the liver enzymes glutathione-S-transferase, glutathione peroxidase and catalase (P < 0.001), which showed a depression following exposure to the carcinogen. The results suggest a preventive role of water-soluble constituents of M. charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of the biotransformation and detoxification system of the host.