Through immunohistochemical studies we have identified the cell-surface proteoglycan, NG2, on blood vessels throughout the rat embryo. The particular cell type expressing this chondroitin sulfate proteoglycan, however, is dependent upon tissue location. Microvessels within the rat CNS express NG2 on endothelial cells, while in blood vessels outside the CNS, NG2 is found on smooth muscle cells. To analyze what role NG2 might play in these blood vessels, an enzymatic dissociation protocol was used to establish primary cultures of vascular smooth muscle cells from Postnatal Day 3 rat aorta. In this study we demonstrate the involvement of NG2 in the mitogenic and chemoattractant responses of smooth muscle cells to PDGF. In assays measuring either DNA synthesis or cell migration, treatment of smooth muscle cells with anti-NG2 immunoglobulins decreased their responses to PDGF-AA but had no effect upon their ability to react to PDGF-BB. These results support a role for NG2 in potentiating signaling through the alpha PDGF receptor in vascular smooth muscle cells. The presence of the proteoglycan on a large subpopulation of these cells could provide an enhanced response to the growth factor in times of active normal growth or in pathological conditions, such as arterial injury or atherosclerosis.