We investigated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in rat vascular smooth muscle cells (VSMC) and in human atherosclerotic arteries to test the involvement of MCP-1 in the pathogenesis of atherosclerosis. In Northern blot analysis, MCP-1 mRNA expression was not observed in unstimulated cultured rat vascular smooth muscle cells (VSMC), but its expression was clearly observed by exposure to tumour necrosis factor-alpha (100 U/ml) for 2-6 h. Mitogen-activated protein kinase activity in VSMC incubated in serum-free culture medium was increased by exposure to 0.5% fetal bovine serum, while the effect was significantly suppressed in the presence of MCP-1 (100 ng/ml). We then evaluated MCP-1 mRNA expression in atherosclerotic arteries obtained from 12 patients undergoing bypass revascularization through reverse transcription-polymerase chain reaction analysis and observed MCP-1 mRNA expression in all atherosclerotic arteries studied. These results support the premise that MCP-1 is secreted by VSMC in atherosclerotic plaques as well as by endothelial cells and macrophages and contributes to the pathogenesis of atherosclerosis.