Epidemiological studies suggested that above average intake of beta-carotene (betaC) might reduce cancer risks. However, clinical trials found that betaC supplementation did not reduce the occurrence of non-melanoma skin cancer and that smokers suffered a significant increase in lung cancer incidence. Further, supplementing semi-defined diets with betaC failed to provide photoprotection as reported earlier for closed-formula rations, but actually exacerbated carcinogenesis. A redox mechanism, based upon one-electron transfer rate constants, proposed interactions between tocopherol, betaC and ascorbic acid in which the carotenoid radical cation, a strongly oxidizing radical, would be repaired by ascorbic acid. If the carotenoid radical cation remained unrepaired, this strongly oxidizing species could account for the pro-carcinogenic activity of betaC. Data from nutritional studies supported an interaction of tocopherol and betaC but not with ascorbic acid. The repair of the betaC radical cation must be dependent on factors other than ascorbic acid, e.g., other carotenoids or unidentified phytochemical(s).