Vascular smooth muscle cells (SMC) transform to foam cells in the process of atherosclerosis. We have reported that SMC derived from the intima of atherosclerotic lesions express c-fms, macrophage colony-stimulating factor receptor gene, which is not normally expressed in medial SMC. In the present study, we demonstrated that transforming growth factor-beta (TGF-beta) synergistically induced expression of c-fms in the presence of platelet-derived growth factor-BB in human medial SMC, a level comparable to that observed in the intima. The induction of c-fms was not inhibited by protein kinase C (PKC) inhibitor, suggesting that TGF-beta induces c-fms via a PKC-independent pathway. These results suggest that TGF-beta plays an important role in the phenotypic change of smooth muscle cells to macrophage-like cells in the process of atherosclerosis.