To define the effects of moderate alcohol intake on cholesterol and triglyceride metabolism in man, twelve patients were hospitalized on a metabolic ward and were fed defined diets for 10 weeks. Each patient underwent testing of plasma lipid and lipoprotein levels, of cholesterol metabolism (absorption, fecal excretion, bile saturation), and of triglyceride metabolism [turnover of triglycerides in chylomicrons and very low density lipoproteins (VLDL)]. This testing was done twice, first during a 4-week control period and then during a 4-week period in which 630 calories of alcohol were either added to or substituted for baseline calories. This increased the average baseline caloric intake by only 24% (range 20% to 30% depending on the initial caloric intake). Addition of alcohol to the baseline diet did not cause weight gain in lean individuals. Obese individuals' responses were more variable, and 3/6 definitely gained weight when the diet was supplemented with alcohol. In addition, obese subjects appeared to be more susceptible to the hyperlipidemic effects of alcohol; whereas 4/6 obese patients developed increased total triglyceride and VLDL-triglyceride concentrations when alcohol was administered, concentrations increased with alcohol administration in only 1/6 lean individuals. High density lipoprotein (HDL) cholesterol increased in all volunteers. Low density lipoprotein (LDL) levels did not change. Metabolic studies showed increased transport of VLDL-triglycerides in overweight patients but not in normal weight individuals; increased transport of VLDL-triglycerides in the former was associated with delayed clearance of chylomicron triglycerides. Alcohol consumption did not affect lipoprotein lipase or hepatic triglyceride lipase in six patients in whom these enzyme activities were measured. In the amounts of alcohol taken in this study, no changes were observed in absorption, synthesis, or excretion of bile acids, or percent saturation of gallbladder bile with cholesterol.