Ozone reacts with polyunsaturated fatty acids (PUFAs) in vitro to form free radicals, and vitamin E slows or prevents this reaction. Consistent with this, dietary vitamin E significantly protects animals against the deleterious effects of ozone and the absence of vitamin E potentiates damage by ozone. Thus, chemical and animal studies as well as the opposite effects of ozone and vitamin E on the immune system suggest the hypothesis that vitamin E can protect humans against the harmful effects of chronic exposures to ozone. However, because most humans are not vitamin E deficient, the more relevant question is whether amounts of vitamin E above the minimum of dietary requirement provide increased protection. The need for and design of further studies to answer this question are discussed.