Studies with rabbits have shown that the nature of protein in the diet can influence the concentration of cholesterol in plasma and the severity of arterial lesions. The feeding of animal proteins such as beef protein, casein or fish protein results in a high degree of aortic atherosclerosis. On the other hand, when rabbits are fed on diets containing plant protein preparations such as wheat gluten, corn protein or soy protein, the severity of aortic lesions is minimal. The animal proteins produce higher concentrations of serum cholesterol than the plant proteins. The rise in serum cholesterol induced by the milk protein casein in comparison with soy protein is also found in guinea pigs, pigs, rats, hamsters, but not in domestic fowl, calves and mice. The ultimate aim of such nutrition research with experimental animals is to provide further insight into practical means of decreasing the concentration of plasma cholesterol in man through changes in dietary habits. A decrease in plasma cholesterol will decrease incidence of atherosclerotic disease as manifested, for example, by myocardial infarction. A number of investigators have reported that intake of soy protein in contrast to animal proteins by hypercholesterolaemic patients reduced plasma cholesterol by 0 to 30%. Such studies are often quoted to support the view that the replacement of animal proteins in the diet by vegetable proteins would lower plasma cholesterol in man. However, the intake of soy protein in the studies with hypercholesterolemic patients also involved other changes in the diet, including the elimination of dietary cholesterol and replacement of saturated fatty acids by polyunsaturated fatty acids. In studies in which the type of protein was the only dietary variable, only a small effect or no effect at all of mixed animal proteins or casein over soy protein on plasma cholesterol was seen in healthy subjects while a slightly larger effect was seen in hypercholesterolemic patients. Thus it is questionable whether changes in the nature of protein in man could really contribute to the prevention of atherosclerosis.