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Cigarette smoke contains many xenobiotics, including oxidants and free radicals, which can increase lipid peroxidation. Recently, breath pentane output (BPO) has been recognized as a good indicator of lipid peroxidation. Vitamin E is known to be a potent free radical scavenger which can protect biological membranes against oxidative damage. We investigated the effect of vitamin E (dl-alpha-tocopherol) on lipid peroxidation in 13 healthy smokers. The results showed (1) smokers had increased BPO as compared with 19 healthy non-smokers (16.3 +/- 1.9 vs 5.8 +/- 0.5, pmol/kg body weight/min, p less than 0.001) although both groups had comparable plasma vitamin E and selenium concentrations, (2) supplementation with vitamin E (800 mg/day for 2 weeks) decreased BPO in smokers, and (3) the concentration of plasma selenium-dependent glutathione peroxidase was restored to normal in those smokers (five out of 13) in whom this was low initially. We conclude that a normal plasma concentration of vitamin E does not prevent this increase of lipid peroxidation in smokers but that substantial doses of vitamin E will significantly reduce this increased lipid peroxidation. If a major function of vitamin E is to protect lipids from peroxidation, then smokers have a conditioned insufficiency of vitamin E on a normal diet.