Chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases. The aim of the present study was to evaluate the role of MCP-1, SDF-1, and RANTES polymorphisms as susceptibility markers for systemic lupus erythematosus (SLE) in a group of Mexican patients. MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms were determined in 242 patients with SLE and 220 ethnically matched healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique. The differences between patients and healthy controls were evaluated by chi(2), Fisher's exact test, and Woolf method for odds ratio. A moderately increased frequency of MCP-1-2518 A allele (p = 0.033, pC = NS) and AA genotype (p = 0.017, pC = NS) existed in SLE patients compared with healthy controls. There was a relationship between polymorphisms and some clinical and laboratory characteristics. SLE patients with and without antiphospholipid syndrome demonstrated different distribution of SDF-1 G801A genotype frequencies. On the other hand, patients with leukopenia, anti-dsDNA, and antiphospholipid autoantibodies demonstrated different MCP-1-2518 genotype distribution compared with patients without these features. Our results suggest that MCP-1 polymorphism is moderately associated with the genetic susceptibility to SLE in Mexican individuals. The polymorphisms could be related to specific clinical and laboratory characteristics in these patients.