Alcohol consumption is associated with high levels of high-density lipoproteins (HDLs). Moreover, changes in the fatty acid patterns of red blood cell phospholipids and plasma lipids have been observed in drinkers. The objectives of this study were to characterize the composition of HDL particles with respect to lipid molecular species in regular wine drinkers and to assess the functional properties of those HDLs as regards key steps of reverse cholesterol transport. Forty-six subjects were recruited in the frame of a population study performed in Toulouse, southern France, and a nutritional investigation, including daily alcohol consumption, was performed. Subjects were sorted according to their daily alcohol intake (0, < or =35, and >35 g/day), mostly as red wine. The plasma HDL fraction was isolated, and neutral lipid molecular lipids and phospholipid fatty acids were analyzed by gas liquid chromatography. Efflux of cellular cholesterol and rates of cholesterol esterification and cholesteryl ester transfers between lipoproteins were assayed in a cell-plasma incubation system. Wine drinking, at 47 g/day, was associated with an increase in HDL cholesterol and apolipoprotein A-I, but not with triglycerides. Isolated HDL displayed a 27% increase in all cholesteryl ester molecular species. The particles were also enriched in unsaturated phospholipids and, particularly, in those containing arachidonic (+30%) and eicosapentaenoic (+90%) acids. The plasma cholesterol esterification rate, reflecting lecithin cholesterol acyl transferase activity on HDL, was found to be higher (+27%) in drinkers than in nondrinkers, whereas the rate of cellular cholesterol efflux to plasma was identical. Regular wine consumption is associated with high levels of polyunsaturated lipids in HDL and with increases in the cholesterol esterification rate.