Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to destruction of cartilage and bone. Chemokines, molecules able to induce chemotaxis in inflammation, are involved in RA pathogenesis. Aim of this study was to determine whether -2150 A>G and delta32 (Δ32) polymorphisms in the chemokine receptor 5 (CCR5) confer susceptibility to rheumatoid arthritis. Polymorphisms were assessed in 70 seropositive RA patients and 200 healthy individuals of Messina and province. About -2150 A>G polymorphism, a significant increase in AG genotype frequency was observed in controls than in patients, despite a not significant difference in allelic frequencies. Conversely, allelic and genotypic frequencies related to Δ32 polymorphism were significantly higher in controls group than in patients. Furthermore, in the patient group no individuals with Δ32/Δ32 genotype were found. These results suggest that CCR5 polymorphisms seem to play an important role in susceptibility to RA exerting a protective role in the disease.