Lipoprotein cholesterol data from the Framingham Heart Study show that low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels are important in determining risk for coronary artery disease (CAD). Increased LDL and decreased HDL cholesterol levels are associated with an increase in CAD. Such relations are independent of the usual coronary risk factors, such as cigarette use and hypertension. A 1% greater LDL value is associated with slightly more than a 2% increase in CAD over 6 years; a 1% lower HDL value is associated with a 3 to 4% increase in CAD. Even at total cholesterol levels <200 mg/dl, lower HDL levels are associated with increased myocardial infarction rates in both men and women. Death from CAD is increased when HDL levels are low, but there is no such relation between HDL level and cancer death. Triglyceride levels were associated with CAD in Framingham men and women, but the association was no longer significant in men after adjustment for HDL levels. The major determinants for greater HDL levels in Framingham participants included female sex, estrogen use, leanness, greater alcohol intake, exercise, abstinence from smoking and lack of diuretic or β-blocker use.