The reduction of cardiovascular mortality associated with moderate alcohol consumption is chiefly thought to be mediated by an increase of high density lipoprotein cholesterol (HDL-CH). This study highlights additional qualitative changes of HDL that might augment this antiatherogenic effect. In 279 healthy men, alcohol and nutrient consumption were evaluated. Groups 1 (n = 62), 2 (n = 172), and 3 (n = 45) comprised subjects with alcohol consumption of 0-5.0, 5.1-30.0, and 30.1-75 g/day, respectively. Lipid analysis was performed in nonfractionated and fractionated plasma, including subfractions HDL_2a, HDL_2b, and HDL₃. No difference in LDL-cholesterol was observed. Compared with group 1, groups 2 and 3 exhibited significant increases of HDL-CH (group 1, 44 ± 10 mg/dl; group 2, 51 ± 11 mg/dl; group 3, 55 ± 11 mg/dl; mean ± SD, P < 0.0005), accompanied by enhanced lipidation of HDL (increase of the HDL₂-CH/HDL₃-CH ratio). Moreover, phospholipid enrichment of HDL occurred in alcohol consumers, whereas the ratios between other HDL components remained constant. Multivariate analysis revealed alcohol to have the foremost statistical influence on changes of the HDL fraction, followed by body mass index and physical activity level. The increased lipidation of HDL found in alcohol consumers might augment the antiatherogenic effect of HDL-CH increase. In addition, the phospholipid enrichment of HDL might reduce the inflammatory response of atherogenesis.