An association study and a linkage analysis were carried out in parallel in order to investigate the association of the inducible nitric oxide synthase (NOS2) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition and/or outcome including a -954G-C mutation, a di-allelic (TAAA)(n) marker and the highly polymorphic (CCTTT). The -954G-C point mutation occurred non-polymorphic and the di-allelic (TAAA)(n) marker was not associated with RA predisposition. The (CCTTT)(n)locus showed a trend for RA association in the case-control study, however, stratification data by Class II status did not yield significant effect and overall, the family study showed no significant association nor linkage for any of the markers under study using TDT and non-parametric linkage respectively. Finally, no influence was detected regarding any of the clinical parameters tested. After evaluating for the first time the influence of NOS2 promoter polymorphism in RA, it seems to have no major effect on disease susceptibility and/or outcome.