In erythrocytes from diabetic patients, increased membrane lipid peroxidation might lead to abnormalities in composition and function. To study this relationship, we investigated the effects of a moderate pharmacologic dose of vitamin E for 1 y on erythrocyte membrane peroxidation in vitro and on its fatty acid composition, antioxidant capacity and rheological function. In a random and double-blind manner, type 1 diabetic patients (n = 44) were assigned to the following two groups: Group S received 250 IU (168 mg) d-alpha tocopherol 3 times daily for 1 y. Group P received placebo for 6 mo followed by d-alpha-tocopherol for an additional 6 mo. Variables were monitored every 3 mo. After 3 mo of supplementation, serum vitamin E doubled (P < 0.0005), thiobarbituric acid reactive substances in erythrocyte membranes incubated with tert-butyl hydroperoxide decreased by 25% (P = 0.006) and the lagtime of fluorescence increased from 28 +/- 16 to 41 +/- 28 min (P = 0.028). Patients who did not respond to supplementation (13 of 44) had lower serum lipids (P = 0.017) and body mass index (P = 0.024). We did not detect any significant effects of vitamin E supplementation on membrane lipid composition, antioxidant capacity or blood viscosity. Continuing supplementation for up to 1 y did not further affect serum vitamin E or membrane peroxidation. Stopping supplementation was followed by a return to inclusion values. These results show that the decrease in erythrocyte membrane peroxidation after vitamin E supplementation is moderate, saturable, reversible, restricted to some individuals and has no detectable effect on erythrocyte composition and function.