Several lines of evidence suggest that free radical-mediated oxidative damage to lipoproteins may be an important factor predisposing them to uptake into the vascular wall. This has led to interest in the factors that determine the susceptibility of lipoproteins to oxidation and their relationship to the development of coronary heart disease. Of these factors, the lipoprotein content of natural antioxidant vitamins such as vitamin E, and beta-carotene have aroused particular interest. Studies in animal models of atherosclerosis suggest that natural and synthetic antioxidants can retard the development of atheroma. Epidemiological comparisons between populations and studies within populations also support the contention that high plasma levels or dietary intake of natural antioxidant vitamins may protect against the development of coronary disease in man. Prospective randomized controlled trials of antioxidants in high risk groups are underway to test whether the theoretical promise of a beneficial role for antioxidants in coronary heart disease prevention will be fufilled.