Leflunomide is an isoxazole derivative that is structurally and functionally unrelated to other known immunomodulatory drugs. Previous studies have revealed that therapy with leflunomide causes decreased production of mediators such as IL-1beta, IL-6, and TNF-alpha, which are involved in inflammatory process. The aim of the present study was to examine whether the polymorphisms in genes IL1B, IL6, and TNF may affect treatment outcomes in RA patients treated with leflunomide. The study was carried out on 129 patients (106 women, 23 men, mean age 52.9 +/- 11.03) diagnosed with RA and treated with leflunomide 20 mg daily. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% and 50% response criteria. There were no statistically significant associations between the studied genotypes and improvement of disease activity parameters. The results of the present study suggest that IL1beta, IL6, and TNF gene polymorphisms are not significant factors influencing the therapy outcome of RA patients with leflunomide.