Risk of coronary heart disease over 14 years was examined prospectively in 2,282 men and 2,845 women according to their antecedent cholesterol and lipoprotein status. An increased risk proportional to antecedent serum cholesterol was found whether or not it was associated with elevated S_f20-400 prebeta lipoprotein. When adjustment was made for the concomitant prebeta lipoprotein concentration and other factors related both to coronary heart disease risk and to blood lipids, a residual gradient of coronary heart disease risk proportional to the serum cholesterol was still evident. On the other hand, when risk of coronary heart disease was examined according to prebeta lipoprotein concentration, adjusting for cholesterol, no residual risk gradient remained in men. In women over 50, however, prebeta lipoprotein was superior to cholesterol in discriminating potential coronary heart disease cases. Risk of coronary heart disease in men can be estimated using any of the lipids evaluated: however, none proved more useful than an accurate total serum cholesterol.