Blood lipids have been established as fundamental to atherogenesis, and there is a better understanding of the pathogenesis of atherosclerosis and of the various pharmacologic agents available to counter the mechanisms involved. However, more optimal lipid levels must be established for treatment of both the healthy population and persons already with coronary artery disease (CAD). In the Framingham Study cohort, those with elevated serum total cholesterol (> 275 mg/dl) had an increased risk of adverse outcomes whether healthy or with CAD. Compared with persons with cholesterol levels < 200 mg/dl (< 5.17 mmol/liter), the risk ratios for patients with elevated cholesterol levels were 3.8 for reinfarction, 2.6 for CAD mortality, and 1.9 for overall mortality. The prevalence of cholesterol levels > or = 240 mg/dl (> or = 6.21 mmol/liter) in persons who had sustained myocardial infarction was 35-52% in men and 66% in women, but 20% of myocardial infarctions occurred in people who had cholesterol levels < 200 mg/dl (< 5.17 mmol/liter). The average levels of serum total cholesterol and low density lipoprotein (LDL) cholesterol (225 mg/dl [5.82 mmol/liter] and 150 mg/dl [3.88 mmol/liter], respectively) at which CAD events occurred in men were below the levels recommended for treatment according to the guidelines of the National Cholesterol Education Program. In women, these levels were only slightly above the guideline levels. The average cholesterol levels at which CAD events occurred were substantially higher in women and decreased with age. Also, a steady decline in the average cholesterol levels of patients over the decades reflected chiefly the aging of the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)