AbstractThe statistical correlation between elevated serum cholesterol levels and increased risk of coronary heart disease has channeled thinking towards regarding dietary fat and cholesterol as the principal causes of hypercholesteremia. Since 1909 there have been a number of changes in nutrient availability in the United States. Protein availability is unchanged but the ratio of animal to vegetable protein rose from 1.06 in 1909 to 2.37 in 1972. Fat availability has risen by 26% with the ratio of animal to vegetable fat falling from 4.88 in 1909 to 1.64 in 1972. A review of available data indicates that amount and type of protein may affect cholesteremia and atherosclerosis in experimental animals. Soy protein is less cholesteremic than casein but the extent of difference can be affected by the type of carbohydrate. In a semi‐purified, cholesterol‐free diet, saturated fat exerts an atherogenic effect but unsaturated fat does not. No atherogenicity is evident when saturated fat is added to laboratory ration. In the semipurified diet, fructose is more atherogenic than glucose, and casein is more atherogenic the soy protein. The latter difference can be virtually eliminated if alfalfa raplaces cellulose as the ditary fiber. The data suggest that all elements of the diet interact and can affect cholesteremia and atherosclerosis. These effects must be considered in the planning of dietary intervention trials.