The body cholesterol pool increases with decreasing plasma-high-density- lipoprotein (H.D.L.), but is unrelated to the plasma concentrations of total cholesterol and other lipoproteins. This finding supports existing evidence that H.D.L. facilitates the uptake of cholesterol from peripheral tissues and its transport to the liver for catabolism and excretion. Plasma-H.D.L. is reduced in several conditions associated with an increased risk of future ischæmic heart-disease (I.H.D.), namely hypercholesterolæmia, hypertriglyceridæmia, male sex, obesity, and diabetes mellitus, while subjects with existing clinical I.H.D. have lower levels of H.D.L. than healthy subjects within the same community. It is proposed that a reduction of plasma-H.D.L. concentration may accelerate the development of atherosclerosis, and hence I.H.D., by impairing the clearance of cholesterol from the arterial wall.