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 α 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 protein. 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.