The aim of this study was to assess the oxidative stress status in rheumatoid arthritis (RA) by measuring markers of free radical production, systemic activity of disease, and levels of antioxidant. 52 RA patients and 30 healthy controls were included in the study, and clinical examination and investigations were performed and disease activity was assessed. Peripheral blood samples were used for all the assays. We assessed the markers of oxidative stress, including plasma levels of index of lipid peroxidation-thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), superoxide anion radical (O-2 (-)), nitric oxide (NO), and superoxide dismutase activity (SOD), catalase activity (CAT) and glutathione levels in erythrocytes. In the RA group, levels of H2O2, O-2 (-), and TBARS were significantly higher than in controls (4.08 +/- A 0.31 vs. 2.39 +/- A 0.13 nmol/l, p < 0.01; 8.90 +/- A 1.28 vs. 3.04 +/- A 0.38 nmol/l, p < 0.01, 3.65 +/- A 0.55 vs. 1.06 +/- A 0.17 mu mol/l, p < 0.01). RA patients had significantly increased SOD activity compared with healthy controls (2,918.24 +/- A 477.14 vs. 643.46 +/- A 200.63UgHbx103, p < 0.001). Patients had significantly higher levels of pro-oxidants (O-2 (-), H2O2, and TBARS) compared to controls, despite significantly higher levels of SOD. Significant differences were also observed in serum levels of NO in patients with high-diseases activity. Our findings support an association between oxidative/nitrosative stress and RA. Stronger response in samples with higher diseases activity suggests that oxidative/nitrosative stress markers may be useful in evaluating the progression of RA as well as in elucidating the mechanisms of disease pathogenesis.