Objective: Adequate dietary intakes of vitamin E and essential polyunsaturated fatty acids are important to maintain cell membrane integrity, and de®ciencies have been associated with smoking related cardiovascular disease. Suf®cient vitamin E is required to prevent free radical mediated peroxidation of membrane lipids. Consequently, smokers may have a greater requirement for this antioxidant. To investigate, we assessed the concurrent in¯uences of smoking, vitamin E supplementation and red blood cell (RBC) PUFA composition on the susceptibility of the cells to lipid peroxidation in adult males. Design and subjects: Thirty male smokers and thirty male non-smokers were randomly ascribed to daily 280 mg vitamin E or placebo supplements for 10 weeks. RBC were analysed at weeks 0 and 10 for fatty acid methyl esters, vitamin E, and their susceptibility to in vitro H 2 O 2 induced lipid peroxidation. Results: Concentrations of essential fatty acids (EFA) in RBC were lower in smokers than in non-smokers. Supplementation with vitamin E increased levels of RBC EFA in smokers to match those of non-smokers. Furthermore, the ratio of vitamin E to PUFA in RBC from smokers and non-smokers was inversely correlated with their susceptibility to peroxidation. Conclusions: An adequate vitamin E to PUFA ratio is required to protect cell membranes from oxidative damage. The signi®cant correlation between susceptibility to peroxidation and the PUFA content of RBC before supplementation suggests an inadequate intake of vitamin E in relation to PUFA intake. Moreover, the requirement for vitamin E appears to be greater in smokers than in non-smokers.