Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Previous studies by this laboratory have shown that exposure to workplace ETS results in increased oxidative stress and damage, as measured by increased levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. 8-Hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was also 63% greater in the exposed group compared with controls. Subjects in the previous study who reported workplace exposure to ETS were given a 60-day supply of an over-the-counter antioxidant formulation consisting of 3000 microg of beta-carotene, 60 mg of vitamin C, 30 I.U. of alpha-tocopherol, 40 mg of zinc, 40 microg of selenium, and 2 mg of copper. After the 60-day supplementation period, blood samples were again drawn, and the results were compared with the presupplementation values. A 62% decrease in 8-hydroxy-2-deoxyguanosine was observed after supplementation. Lipid peroxidation levels were also decreased, as were the antioxidant enzyme activities. The biochemical evidence suggests that exposure to ETS in the workplace increases oxidative stress and that antioxidant supplementation may provide some protection.