We investigated the involvement of epidermal lipid peroxidation in the induction of ultraviolet radiation (UVR)-induced suppression of the skin immune system. The shaved dorsal skin of C3H/HeJ mice was irradiated with one of two subinflammatory solar-simulated UVR protocols 3 days per week for 4 weeks. Then half of 1 mg, 1, 2.5 or 5 mg alpha-tocopherol in a vehicle of acetone was topically applied to the shaved dorsal skin before UVR, A 5 mg dose of vitamin E gave complete protection against a UVR protocol that induced a 55% reduction in the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene and a 23% reduction in epidermal Langerhans cell density. Lower doses were ineffective. alpha-Tocopherol was unable to protect against a higher UVR protocol. As 5 mg alpha-tocopherol did not prevent postirradiation inflammatory edema it is unlikely that the antioxidant acted as a sunscreen. However, 5 mg alpha-tocopherol inhibited UVR-induced epidermal lipid peroxidation, suggesting that this may be one mechanism by which alpha-tocopherol prevented UVR-induced local immunosuppression. Scavenging of UVR-generated lipid peroxides and reactive oxygen may have inhibited loss of cell membrane integrity preventing depletion of LC numbers, thus protecting from local immunosuppression.