The involvement of inflammatory mechanisms in the progression of atherosclerosis has recently been suggested. Monocyte chemotactic protein 1 (MCP-1) is a soluble protein which is implicated in acute and chronic inflammatory processes, including atherosclerosis. We evaluated the effect of human recombinant MCP-1 on the in vitro proliferation of rat vascular smooth muscle cells (VSMCs). Incubation of VSMCs with MCP-1 (50-200 ng/ml) in the presence of 0.5% FCS significantly increased cell proliferation, [3H]-thymidine incorporation and the proliferative S fraction, measured by flow cytometry, compared to control cells. The proliferative effect of MCP-1 was specific, as shown by inhibition with a rabbit polyclonal serum to MCP-1. Moreover, the mitogenic effect of MCP-1 was significantly inhibited by downregulation of protein kinase C (PKC) activity and by incubation with H-7, a protein kinase inhibitor, suggesting the involvement of the PKC system. Verapamil, a Ca2+ channel blocker, also reduced the stimulatory effect of MCP-1 on cell proliferation. This study demonstrates that MCP-1 does not merely have a chemotactic activity, but also a mitogenic effect on cultured rat VSMCs.