More than one-third of patients with coronary disease have "low" high density lipoprotein cholesterol (HDLc) levels (less than 35 mg/dl; United States 20th percentile) and "normal" low density lipoprotein cholesterol (LDLc) (less than 145; United States mean), a group for whom current treatment guidelines are not based on clinical trial data. Low HDLc levels are strong, independent predictors of cardiovascular disease and cardiovascular mortality risk, equally so for both men and women. This high coronary artery disease risk may be due to an imbalance between delivery of cholesterol into the arterial intima by LDL and its removal by HDL. Also, since HDL serve as antioxidants and cytoprotectants, an important HDL role may be to prevent LDL oxidation and thus limit macrophage-mediated intimal lipid accumulation or to prevent vascular cell toxicity. Recent epidemiologic, experimental, and clinical trial evidence suggests that a 15 mg/dl rise in HDL cholesterol would reduce coronary artery disease incidence and mortality by 30 to 70 percent and that antioxidant vitamins E, C, and beta-carotene might reduce coronary artery disease events and atherogenesis. The potential absolute benefit is much greater in those with existing coronary artery disease. It has also been shown that HDLc rises in response to exercise, smoking cessation, weight reduction, and monounsaturated fats.