Chemokines are critical for the inflammatory process in autoimmune diseases such as rheumatoid arthritis (RA). The chemokine receptor-5 (CCR5) mediates chemotaxis by CC-chemokines and is expressed by lymphocytes with the Th1 phenotype and monocyte/macrophages. A 32 bp deletion in the CCR5 (CCR5-Δ32 allele) abolishes receptor expression in homozygotes, while CCR5-Δ32 carriers would express less receptor than wild-type homozygotes. This polymorphism is related to the resistance to HIV-1 infection and progression towards AIDS. We hypothesized that the CCR5-Δ32 allele may modulate the severity of disease in RA. A total of 160 RA-patients (71 and 89 with severe and non-severe phenotypes, respectively) and 500 healthy individuals from the same Caucasian population (Asturias, northern Spain) were genotyped. Carriers of the CCR5-Δ32 allele were at a significantly higher frequency (P= 0.012) in non-severe compared to severe patients (17% vs 4%). Our results suggest that the CCR5-Δ32 polymorphism is a genetic marker related to the severity of RA.