We have compared the inhibitory effects of plasma lipoproteins on DNA synthesis by phytohemagglutinin-stimulated rat lymphocytes. The order of suppressor potency was: very low density lipoproteins (VLDL) > chylomicrons > low density lipoproteins > > high density lipoproteins. We have further demonstrated the presence of specific receptor sites for VLDL on rat spleen lymphocytes. The number of VLDL receptors was estimated at 31,000 by a modified Scatchard analysis. Our results suggest that in the normal physiologic state, the proliferation of circulating lymphocytes may be suppressed by the combined effects of plasma lipoproteins. Furthermore, it would appear that the binding of plasma VLDL to specific receptors on rat lymphocytes would be the initial physiological event in this inhibitory process.