Three classes of lipoproteins, very low, low, and high density, were isolated from normal mouse sera and characterized with respect to electrophoretic mobility, content, and composition. All 3 classes of mouse serum lipoproteins migrated into the alpha region at different rates and were composed of more phospholipid and less triglyceride and cholesterol than lipoproteins from man. High density lipoprotein (HDL) was the major lipoprotein, carrying 70% of the serum cholesterol and phospholipid and 85% of the total lipoprotein. Whole mouse serum and all classes of mouse serum lipoproteins inhibited lymphocyte proliferation stimulated by mitogens. No strain specificity was observed. HDL contributed about 73% of the total inhibitory activity. The effect of apoprotein and the lipid portion of very low, low, and high density lipoproteins were also studied.