Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to evaluate the -590 IL-4 promoter polymorphism in patients with RA and its association with disease activity and severity. We enrolled 94 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the polymorphism at position -590 of the promoter of the IL-4 gene. The distribution of IL-4 genotypes in RA patients did not differ from control subjects. Nevertheless, the active form of RA was more frequently diagnosed in patients with T allele (genotypes CT and TT) as compared with homozygous CC patients. Moreover, in carriers of the T allele, parameters of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. We suggest that the IL-4 -590 promoter polymorphism may be a genetic risk factor for RA severity.