Rats were fed semipurified diets, differing in the amount of cholesterol and the sources of fat (corn oil or coconut fat) and carbohydrate (sucrose or starch). After 21 days dietary corn oil had induced higher serum cholesterol concentrations than did coconut fat, except for on diets with a high-cholesterol, high-sucrose background. On high-cholesterol diets containing coconut fat, dietary sucrose increased serum cholesterol, when compared with starch; with corn oil sucrose tended to lower serum cholesterol. Such a tendency was not seen on cholesterol-free diets. Cholesterol feeding caused a dramatic increase in liver cholesterol with all dietary carbohydrate-fat combinations. Liver cholesterol was higher in rats fed corn oil than in those fed coconut fat. The influence of the type of dietary carbohydrate on liver cholesterol was dependent on the type of fat and the amount of cholesterol in the diet. Thus effects of a single dietary component on serum and liver cholesterol in rats are strongly influenced by the background of the diet. This implies that published results of experiments on diet and cholesterol metabolism in rats cannot be compared readily.