High-density lipoproteins (HDLs) play an important role in the process of reverse cholesterol transport, the pathway by which the cholesterol in extrahepatic tissues is transported through plasma to the liver for recycling or for excretion from the body in bile. The concentration of HDL cholesterol is a powerful inverse predictor of the development of coronary heart disease, leading to a widely held view that HDL protects against the development of atherosclerosis. The mechanism by which HDLs protect is unknown. To date, no studies have been designed specifically to test the proposition that increasing the concentration of HDL cholesterol translates into a reduction in coronary risk. Nevertheless, in a subgroup of the Helsinki Heart Study, it was found that a substantial proportion of the beneficial effect of gemfibrozil was explicable in terms of an increase in the concentration of HDL cholesterol.