Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis.