The effect of ethanol on serum cholesterol concentration has been studied in normal male dogs subsisting on diets of low cholesterol content. Daily administration of 1.65 Gm. ethanol/Kg, of body weight produced significant increases of serum cholesterol in dogs when fed either a low-fat diet (4 per cent of fat calories) or a high-fat (40 per cent) diet. The mean cholesterol increase after 2 weeks of ethanol administration was 52 mg./100 ml. (SE, 8.2) for 8 dogs on the low-fat diet, and 75 (SE, 6.6) for 24 dogs on the high-fat (lard) diet. No significant difference was found between the mean increases of serum cholesterol produced by ethanol administration, using either the high-fat diet of saturated fat (lard) or that of unsaturated fat (sunflower oil). Serum cholesterol concentration decreases rapidly after discontinuing the administration of ethanol, reaching the prealcohol levels in 2 to 3 weeks. The higher levels of serum cholesterol are maintained as long as the administration of ethanol continues. Sodium acetate, when given at the same molar quantity as ethanol, failed to produce any change of serum cholesterol concentration in the dog.The effect of ethanol administration on serum cholesterol concentration in man was tested in 2 switchback experiments, comparing the effects of alcohol and those of a supplement of syrup of equal calorie value while the men were eating a normal diet containing 38 per cent of fat calories. When 0.45 Gm. ethanol/ Kg./day were given to 59 normal men for 3 weeks, no significant difference of serum cholesterol concentration was observed between the values on syrup and on alcohol. However, the administration of 1.35 Gm./Kg./ day to 14 men produced a mean increase of serum cholesterol concentration of 18 mg./100 ml. (SE, 5.0) within 1 week. The individual increases of serum cholesterol are correlated with the intrinsic cholesterol levels of the subjects (r = + 0.67, p > 0.01). It is concluded that ethanol increases serum cholesterol concentration in the dog and man. The response in the dog is much greater than that observed in the human subjects.