The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttranslational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholesteryl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p < 0.01), but without significant difference between the apo E groups. In conclusion, alcohol abuse does not cause major changes in the electric charge of apo E in humans. Heavy alcohol intake seems to have a beneficial effect on plasma lipids and lipoproteins, regardless of the apo E phenotype, but the modulation of the alcohol-induced increase in HDL by apo E phenotype should be taken into consideration in future studies.