Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with HLA-DR genes that share amino acid sequence motif QKRAA/QRRAA from position 70 to 74 in the third hypervariable region of DR1 molecule. The contribution of HLA in RA is however about 37%, suggesting a role for other genes. One such candidate is the gene that encodes natural resistance-associated macrophage protein (NRAMP1), which plays a crucial role in inflammation and tissue destruction. In the present study, we examined the role of NRAMP1 gene polymorphisms in susceptibility to RA. The results show that variation at position 543 in exon 15, which involves substitution of negatively charged aspartic acid (D) by uncharged asparagine (N), and the deletion of TGTG in the 3' UTR may confer protection from development of RA.