In animals, ingestion of casein, the principal protein in milk, causes hypercholesterolemia, whereas in humans this effect has not been documented. We added 27 g of casein (the amount in 1.1 liters of skim milk and nearly twice the average U.S. intake) for 20 days, and 27 g of soy protein for an additional 20 days to the daily diet of 13 strict vegetarians who consumed no other animal protein during the study period. The protein supplementation increased the ad libitum daily protein intake from 59 g to 82 g. Levels of plasma LDL, HDL, and total cholesterol were not significantly affected by either the casein or the soy supplementation. Over the 40 days of protein supplementation, there were progressive decreases in VLDL cholesterol (VLDL-C) and increases in triglycerides (TG) from pre-study levels, demonstrated by an overall change in the VLDL-C/TG ratio from 0.30 to 0.17 (P = 0.003). Caloric intake and body weight did not change significantly. From the literature on dietary protein and blood lipid levels and from the present data, it appears that neither the amount of protein in the diet nor whether the protein comes from animal or vegetable sources has an important effect on plasma LDL and HDL levels in humans when consumed in physiologic amounts.