The effect of dietary plant protein vs animal protein on plasma lipoproteins was investigated in a crossover study. Eleven normal subjects consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat, and 53% as carbohydrate: the average cholesterol intake was 500 mg/d. After an initial decrease in plasma cholesterol and low-density-lipoprotein cholesterol (LDL-C) on both diets, the concentration of LDL-C stabilized during the soy-protein diet at a 16% lower level than on the casein diet (p less than 0.02) whereas the concentration of high-density-lipoprotein cholesterol (HDL-C) was 16% higher (p less than 0.01). In a similar earlier study with a cholesterol intake of less than 100 mg/d, casein and soy protein had indistinguishable effects on lipoprotein levels. Our two studies together suggest that the level of cholesterol intake may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL and HDL concentrations.