David J. Gordon National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland I. INTRODUCTION Although the etiologic role of cholesterol in coronary atherogenesis is well established, and clinical trials of cholesterol-lowering drugs have confirmed that this process can be slowed or even partially reversed by treatment, the net effect of cholesterol lowering on mortality was in doubt as little as 4 years ago (1). Clinical trials using bile acid sequestrant resins, fibrates, niacin, diet, and hormones to lower cholesterol suffered from a combination of modest cholesterollowering efficacy, side effects, poor compliance, and inadequate sample size, and often gave equivocal results, with favorable trends in the incidence of myocardial infarction (MI) and other clinical sequelae of atherosclerotic coronary heart disease (CHD) offset by unfavorable trends in non-CHD mortality.