Oxygen free radicals have been shown to result from and mediate deleterious effects of ultraviolet radiation on the skin. The purpose of this study was to determine if topical DL-alpha-tocopherol (vitamin E) could reduce ultraviolet-induced damage to the epidermis. Twenty mice were treated with either ethanol or a 1:1 mixture of tocopherol and ethanol. Treatments consisted of once-daily 0.1-ml topical applications for 1 week, followed by irradiation with 0.30 mW/cm2 of ultraviolet B irradiation. A statistically significant decrease in Schiff base formation was noted between tocopherol-treated animals and their controls. Histologic study revealed a statistically significant increase in epidermal thickness in tocopherol-treated skin versus controls or vehicle alone. The thicker epidermis was accompanied by the presence of parakeratosis, implicating increased proliferation as the cause of the increasing thickness. The number of sunburn cells was decreased by tocopherol treatment. Tocopherol protection from ultraviolet irradiation may have been due to both direct protection from free radicals and indirect protection by means of increased epidermal thickness. The demonstration of beneficial effects of tocopherol administration suggests that further studies in clinically relevant models to define optimal dosage, frequency of administration, vehicle, and quantitation of the possible protective effects afforded to Langerhans cells may be useful.