Monocyte chemoattractant protein-1 (MCP-1) plays an important role in atherosclerosis. Recently, single nucleotide polymorphisms (SNPs) in the MCP-1 regulatory region have been identified, and an in vitro study demonstrated that the SNP at position -2518 of the MCP-1 gene affected transcription of the gene. The purpose of this study was to clarify the association of the plasma level of MCP-1 and the SNP of the MCP-1 gene with carotid atherosclerosis in community-based subjects. The study subjects consisted of 325 community residents, aged 50 years or older (mean age, 70.5 +/- 9.4 years) and free from any cardiovascular complications. Carotid intima-media thickness (IMT) was measured in the right common carotid artery using ultrasonography. The plasma level of MCP-1 was measured by enzyme-linked immunosorbent assay (ELISA). The SNP of the MCP-1 gene was determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. The plasma level of MCP-1 was significantly associated with IMT (r = 0.12, p < 0.05) and carotid arterial dimension (r = 0.13, p < 0.05). There was a significant difference in plasma MCP-1 level between the genotypes (AA, 166 +/- 36 ng/ml; GG + AG, 184 +/- 56 ng/ml; p = 0.036). Analysis restricted to the subjects not receiving antihypertensive drugs or other medication further increased the statistical significance. However, carotid IMT and carotid arterial diameter were not significantly different among the MCP-1 genotypes. Stepwise regression analysis for plasma MCP-1 revealed that the MCP-1 genotype was an independent determinant of plasma MCP-1 level. These findings indicate that plasma MCP-1 is associated with carotid atherosclerosis. Although -2518 SNP is associated with the plasma level of MCP-1, it was not directly associated with carotid atherosclerosis.