High serum concentrations of apolipoprotein (apo) A-I are associated with a decreased risk of coronary heart disease. To study the effect of alcohol intake on serum apo A-I and A-II concentrations, 24 healthy male drinkers (37.8 ±13.9 mL [1.3 ±0.5 oz] of ethanol per day, mean±SD) were randomized into treatment and control groups after a three-week baseline period. The treatment group abstained from all intake of alcohol for the six weeks following randomization and then reverted to its usual level of intake for a five-week period. The control group continued its usual level of drinking throughout the trial. The concentrations of apo A-I and apo A-II of abstainers decreased significantly compared with the corresponding changes in controls. After drinking was resumed, apo A-I and apo A-II concentrations were significantly increased in the treatment group compared with the corresponding changes in the control group. These results suggest that the association between moderate alcohol intake and reduced risk of coronary heart disease may be mediated in part by increased levels of serum apo A-I or apo A-II, or both.