Cholesteryl ester transfer protein (CETP) and apolipoprotein E (apo E) play important roles in reverse cholesterol transport in humans. CETP transfers cholesteryl ester (CE) from high-density lipoprotein (HDL) to other lipoproteins, mainly very low-density lipoprotein (VLDL) remnants, which provide a vehicle for the delivery of HDL-derived CE to the liver via apo E or B/E receptors. Using a sensitive and specific radioimmunoassay, we have demonstrated that plasma concentrations of CETP vary dependent on gender, the concentration and composition of plasma lipoproteins, and dietary cholesterol intake. Plasma CETP appears to increase as an adaptive response to increased peripheral flux of cholesterol. Probucol therapy results in a significant increase in plasma CETP concentration, which may explain, in part, the marked effect of this agent on HDL concentration and composition.