Lipid levels play a central role in determining the predisposition to coronary heart disease. In Western industrialized societies diseases of the heart rank as the number one cause of morbidity and mortality in the adult population. Thirty percent of all deaths in the United States in 1982 were attributable to coronary heart disease. Epidemiological studies of total communities including Framingham, Massachusetts and Tecumseh, Michigan have established a long list of factors that predict increased risk to coronary heart disease. Those that have been implicated include male gender, aging, positive family history, sedentary life style, diabetes, high blood pressure, cigarette smoking, overweight and abnormal plasma levels of lipids and lipoproteins. Although there is great variation among individuals in the risk factors associated with the development of coronary heart disease, the disease typically involves the infiltration of cholesterol into the intimal wall of the arteries beginning early in life. It has been hypothesized that each individual inherits or experiences an array of risk factors that determine susceptibility to the disease process that progresses through the phases of injury to the vascular wall, infiltration of lipids, accumulation of cholesterol esters, a proliferation of cells, stenosis and finally occlusion that leads to the coronary heart disease outcome. Lipid metabolism plays a central role in determining the progression of this process. A role for elevated lipids in the etiology of coronary heart disease is supported by the Lipid Research Clinics trial of cholestyramine which established that a 20 percent reduction of plasma low density lipoprotein (LDL) in particular, results in a 19 percent reduction of coronary heart disease after seven years in high risk males. Most studies to date have focused on environmental factors associated with variability in risk factors. Biometrical studies have estimated the role of genes in determining interindividual variability in lipid and lipoprotein phenotypes by comparing and contrasting the levels in related and unrelated individuals living together and apart. With the advent of new techniques to measure variability in gene products and at the DNA level, it is now possible to expand our studies of the role of genes in both lipid metabolism and coronary heart disease. Knowledge about the genetic epidemiology of coronary heart disease will provide valuable tools for clinical screening and diagnosis and will make it possible to develop a rational strategy to intervene. Not all individuals respond in the same way to lipid-lowering strategies. By knowing the genes involved in regulating the metabolic factors that are altered in coronary heart disease we will be able to sort out those individuals who will respond to specific treatments.