The emerging dogma that low density lipoprotein (LDL) oxidation is a contributing cause and not simply a consequence of atherosclerosis is based on three lines of experimental evidence: (i) lipid peroxidation products and oxidized LDLs are present in atherosclerotic lesions; (ii) oxidized LDL has an array of potentially proatherogenic properties in vitro, including uptake by macrophages via a number of distinct "scavenger" receptors; and (iii) treatment of hypercholesterolemic animals with potent antioxidant drugs can retard the development of atherosclerosis. Additional support for the role of lipoprotein oxidation in atherogenesis was provided by cross-cultural dietary comparisons, which suggested an inverse correlation between antioxidant vitamin intake and coronary mortality. As well, several large case-control studies indicated that antioxidant vitamin intake, particularly vitamin E, was associated with reduced coronary risk. However, these studies do not indicate whether this association is causal, or if vitamin supplementation is merely a marker for some other protective factor. To test this properly, randomized controlled intervention studies are required. In several animal models, a number of different antioxidant drugs have been shown to retard atherosclerosis, but results with vitamin supplementation are unclear. Results of intervention trials in humans show no benefit to long-term beta-carotene supplementation, and the only published study of vitamin E found a reduction of nonfatal myocardial infarction but no reduction (actually an increase) in fatal myocardial infarction and total mortality. Several other large antioxidant intervention trials are underway. Until the results of these studies are available, there appears to be insufficient evidence on which to base recommendations regarding antioxidant supplements for the prevention of atherosclerosis.