A recent review article on the pathogenesis of atherosclerosis stated that the lesions result from an excessive inflammatory-fibroproliferative response to various forms of insult of the endothelium and smooth muscle cells of the arterial wall, that a large number of growth factors participate in this process and that the injury is most apparent at branching points of the arterial tree. We found a significant increase in sphingomyelin and a decrease in other phospholipid components in the arterial wall at the branching points as compared to the non branching points of human and swine arteries. Because of the higher transition temperature of sphingomyelin, its replacement of other phospholipid components may increase the rigidity of the cell membrane and may alter negatively charged bilayers in such a way that they interact more strongly with cholesterol and calcium. Duplication of such conditions with arterial cells in tissue culture caused calcium infiltration into the cell. Furthermore, platelet derived growth factor (PDGF) synthesis was increased in smooth muscle cells grown in magnesium deficient media. It is possible that a change in phospholipid and cholesterol composition of arterial cells at the branching points of arteries and that factors other than PDGF may precede inflammatory-fibroproliferative response to various forms of insult.