In spite of the significant decline in cardiovascular disease (CVD) mortality over the past several decades, CVD remains the leading cause of death in the United States. Although age-specific CVD rates are higher in men than women, CVD is nonetheless the leading cause of death for both sexes, and is responsible for approximately one-third of all fatalities in women as well as men. Antioxidant vitamins are a promising area of current research in the prevention of CVD. The postulated mechanism for such an effect derives from basic research demonstrating the ability of antioxidants to inhibit the oxidation of low-density lipoprotein cholesterol. Epidemiologic studies that have explored the antioxidant vitamin hypothesis include descriptive and cross-sectional studies, analytic investigations using case-control and prospective cohort study designs, as well as several small randomized clinical trials. Findings from these studies are not totally consistent, but generally support the hypothesis that antioxidant vitamins reduce the risk of CVD. Overall, there are fewer data in women than men. Large-scale randomized trials are now ongoing that will provide reliable evidence on this question. The ongoing Physicians' Health Study of over 22,000 men is testing beta-carotene, while the recently begun Women's Health Study of 40,000 women will test, utilizing a factorial design, beta-carotene as well as vitamin E. A trial has also recently been funded to test beta-carotene, vitamin E and vitamin C in secondary prevention among a high-risk population of 8,000 women with prior CVD events.(ABSTRACT TRUNCATED AT 250 WORDS)