β-carotene is a strong singlet oxygen quencher and antioxidant. Epidemiologic studies have implied that an above average intake of the carotenoid might reduce cancer risks. Earlier studies found that the carotenoid, when added to commercial closed-formula rodent diets, provided significant photoprotection against UV-carcinogenesis in mice. Clinical intervention trials found that β-carotene supplementation evoked no change in incidence of nonmelanoma skin cancer. However, when smokers were supplemented with the carotenoid a significant increase in lung cancer resulted. Recently, employing a β-carotene supplemented semi-defined diet, not only was no photoprotective effect found, but significant exacerbation of UV-carcinogenesis occurred. Earlier, a mechanism, based upon redox potential of interacting antioxidants, was proposed in which β-carotene participated with vitamins E and C to efficiently repair oxy radicals and, thus, thought to provide photoprotection. In this schema, α-tocopherol would first intercept an oxy radical. In terminating the radical-propagating reaction, the tocopherol radical cation is formed which, in turn, is repaired by β-carotene to form the carotenoid radical cation. This radical is repaired by ascorbic acid (vitamin C). As the carotenoid radical cation is a strongly oxidizing radical, unrepaired it could contribute to the exacerbating effect on UV-carcinogenesis. Thus, vitamin C levels could influence the levels of the pro-oxidant carotenoid radical cation. However, when hairless mice were fed β-carotene supplemented semi-defined diet with varying levels of vitamin C (0–5590 mg kg−1 diet) no effect on UV-carcinogenesis was observed. Lowering α-tocopherol levels did result in further increase of β-carotene exacerbation, suggesting β-carotene and α-tocopherol interaction. It was concluded that the non-injurious or protective effect of β-carotene found in the closed-formula rations might depend on interaction with other dietary factors that are absent in the semi-defined diet. At present, β-carotene use as a dietary supplement for photoprotection should be approached cautiously.