Heavy alcohol intake causes a marked inhibition of cholesteryl ester transfer protein (CETP) activity resulting in cholesterol ester enrichment of HDL. In this study we have characterized LDL of 35 chronic heavy alcohol drinkers with hyperalphalipoproteinemia to clarify the effect of alcohol on the metabolism of LDL. Serum concentrations of LDL-cholesterol and apolipoprotein B were normal, while the chemical composition of LDL was characterized by depletion of cholesteryl ester and enrichment of triglyceride. The LDL particles of the drinkers were significantly smaller in size than those of controls and had reduced affinity for LDL receptors of normal human fibroblasts. After cessation of alcohol, these abnormal characteristics returned toward normal along with elevation of CETP activity. These results suggest that heavy alcohol intake alters the compositions and particle size of LDL, consequently reducing their affinity for LDL receptors. This may be attributed, at least in part, to the reduction of CETP activity.