The serum cholesterol-lowering effect of dietary soy protein was examined in hypercholesterolemic rats. The inclusion of soy protein in a diet containing cholesterol and casein brought about a reduction in the serum cholesterol levels. A further cholesterol-lowering effect was achieved by increasing the proportion of soy protein in the diet. Conversely, the incorporation of increasing proportions of casein in the diet resulted in an elevation of the serum cholesterol concentration. Changes in serum cholesterol were predominantly reflected in different cholesterol concentrations in the very low density lipoproteins (VLDL). The concentrations of liver cholesterol paralleled the concentrations of cholesterol in the serum. Thus, this study clearly demonstrates that dietary soy protein is able to reduce the levels of cholesterol in the serum and the liver, whereas dietary casein has the opposite effect. Moreover, the cholesterolemic properties of both casein and soy protein can be enhanced by the incorporation of higher proportions of these proteins in the diet.