In animal studies antioxidants have demonstrated antiatherosclerotic actions, but hitherto not in human studies. Prospective epidemiological data suggest that high doses of vitamin E have beneficial effects on major coronary heart disease. Unresolved questions concerning the role of LDL oxidation and antioxidants in atherosclerosis are discussed. It remains to be shown if antioxidants can retard lesion progression in humans, and by what mechanisms they are acting.