DNA damage caused by ultraviolet (UV) irradiation is considered the main etiologic factor contributing to the development of skin cancer. Systemic or topical application of antioxidants has been suggested as a protective measure against UV-induced skin damage. We investigated the effect of long-term oral administration of a combination of the antioxidants ascorbic acid (vitamin C) and D-alpha-tocopherol (vitamin E) in human volunteers on UVB-induced epidermal damage. The intake of vitamins C and E for a period of 3 mo significantly reduced the sunburn reaction to UVB irradiation. Detection of thymine dimers in the skin using a specific antibody revealed a significant increase of this type of DNA damage following UVB exposure. After 3 mo of antioxidant administration, significantly less thymine dimers were induced by the UVB challenge, suggesting that antioxidant treatment protected against DNA damage.