Smokers incur a sustained free radical load which may increase their vitamin E requirement. However, in the present study this was not apparent from plasma and red blood cells (RBC) vitamin E concentrations which were similar in both smokers and non-smokers. However, RBC from smokers were more susceptible to hydrogen peroxide-stimulated peroxidation than those from non-smokers (p<0.001). Furthermore, plasma concentrations of lipid peroxides, thiobarbituric acid reactive substances and conjugated dienes were also elevated in smokers compared with the non-smokers (p<0.05). These indices of oxidative stress were markedly decreased (p<0.001) in both the smokers, and non-smokers, following consumption of 280 mg dl- tocopherol acetate/day for ten weeks. Plasma and RBC vitamin E concentration increased substantially following supplementation, but the % increase in vitamin E required to improve resistance to in vitro RBC peroxidation was significantly greater in non-smokers (p<0.01). This may reflect an endogenous adaptive response to oxidant stress in RBC of smokers. Erythrocyte vitamin E concentrations increased in a dose dependent manner during 20 weeks of supplementation with either 70,140,560 or 1050mg d--tocopherol per day. In smokers each dose was associated with a significant decrease in susceptibility of erythrocytes to peroxidation (p<0.001). However, red cells of non-smokers on the 1050mg supplement demonstrated an increased susceptibility to peroxidation (p<0.001). Thus, vitamin E may demonstrate prooxidant activity in non-smokers at high and prolonged intakes. Moreover, prolonged supplementation with d--tocopherol in non-smokers induced a decline in plasma ascorbate concentration (p<0.02) in association with an increasing erythrocyte vitamin E uptake (p<0,001). Both smokers and non-smokers may benefit from increased vitamin E intakes, although their requirements may be very different. However pharmacological doses may not be required since it appears that doses as low as 70mg are equally effective.