Ecologic studies of vitamin E have shown that regions with relatively low dietary vitamin E tend to have higher rates of coronary heart disease (CHD), but it is difficult to adjust for other risk factors. Cross-sectional studies in individuals have yielded conflicting results, as have prospective studies based on stored blood samples. Two large prospective studies found that persons who had used vitamin E supplements for > or = 2 y had approximately 40% lower rates of CHD. Short durations and doses of < 100 IU/d had no significant effect. The effect of dietary vitamin E was modest and nonsignificant. Adjustment for a wide array of other coronary risk factors had little effect on the findings, which were specific for vitamin E and not other supplements. The only large, randomized trial found no material reduction in CHD risk for 50 IU vitamin E/d. The epidemiologic evidence suggests that high doses of vitamin E may reduce the risk of CHD.