We investigated the effects of dietary plant and animal proteins on high density lipoprotein (HDL) composition of rats fed diets containing either casein or soy protein isolate for 5 weeks. Rats fed casein had increased plasma total cholesterol, triglycerides, very low density and low density lipoprotein (VLDL + LDL) and HDL while HDL cholesterol was unchanged. HDL from casein-fed rats had an increase in percent protein and a decrease in percent cholesterol leading to a decreased cholesterol to protein ratio. Of the individual HDL apoproteins, only the C apoproteins were significantly elevated by casein. In addition, casein-fed rats had an increased proportion of the less sialylated forms of apo C-III. Liver cholesterol was not significantly affected by protein source but was negatively correlated with both HDL cholesterol and HDL protein levels. Addition of cholesterol to the diets largely eliminated any effect of protein source on HDL composition. These data demonstrate that dietary protein source can significantly influence HDL composition despite a lack of effect on HDL cholesterol levels.