Abstract 1. (1) Using both an explant system from swine thoracic aorta and an aortic smooth muscle cell culture system, we have investigated the effect of lipoproteins on the synthesis of DNA in the absence of serum or serum derivatives. 2. (2) Chemical and morphological data from both systems confirm that (a) neither VLDL, LDL nor HDL account for any appreciable part of the DNA synthesis activity of whole serum. (b) There is no difference in activity between lipoprotein fractions derived from either normocholesterolemic or hypercholesterolemic serum. (c) The activity resident in whole serum is present largely in the pelleted serum protein fractions and in the soluble residue. 3. (3) The data suggest that smooth muscle cell proliferation results from the interaction of lipoproteins with other factor(s) in serum.