Epidemiological evidence abounds for a link between intake of carotenoids from fruit and vegetable foods and relatively low incidence of various cancers. However, intervention trials have shown, in some cases, a significant increase in occurrence of lung cancer in those volunteers taking supplements of beta-carotene. More information is clearly needed about the mechanism of action of carotenoids. Effects of carotenoids on cells in culture include inhibition of DNA synthesis and proliferation, changes in gene expression, decreased micronucleus frequency, and inhibition of transformation via synthesis of gap-junction proteins. Experiments with animal models are unsatisfactory because of the very poor uptake of carotenoids in rodents compared with man. In humans, oxidative damage to lymphocytes correlates negatively with plasma carotenoid concentrations, and the level of DNA damage is susceptible to reduction by carotenoid-rich foods. It seems clear that the carotenoids act as antioxidants in vivo, and yet this activity may not result in cancer prevention.