Background Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in atherosclerosis and it has been recently proposed as a surrogate biomarker of long-term clinical outcomes in patients with acute myocardial infarction. Little is known of the factors that may influence plasma MCP-1 concentrations. Methods We studied 384 healthy volunteers and 226 HIV-infected patients as a model of chronic inflammatory condition that predisposes to sub-clinical atherosclerosis. Results In healthy participants there were significant associations between plasma MCP-1 concentration and age, smoking status, and serum triglyceride concentrations that were not observed in the HIV-infected patients. The plasma concentration of MCP-1 was significantly associated with the polymorphism at position –2518 of the MCP-1 gene and, in patients, with the carotid artery intima–media thickness. There were also significant correlations indicating a close association between MCP-1 and HIV disease activity. However, in a multiple regression model, only age, the MCP-1 genotype and smoking status showed significant, and independent, associations with plasma MCP-1 concentrations. Conclusion Plasma MCP-1 concentration is genetically determined and associated with age and smoking habit and it also correlates with subclinical atherosclerosis in HIV-infected patients.