Background: To investigate whether nitric oxide (NO) production correlates with laboratory parameters of disease activity in patients with rheumatoid arthritis (RA), we measured serum nitrates and nitrites (NOx) concentrations, rheumatoid factor (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum iron markers in 115 RA patients. Methods: Serum NOx concentrations were determined after reduction of nitrates to nitrites using the Griess reaction. Serum transferrin receptor (sTfR) and serum ferritin were assayed using an enzyme immunoassay and a chemiluminescence method. Correlation coefficients of CRP, ESR, and RF vs. NOx concentrations were assessed. Results: Serum NOx concentrations averaged 208.3 +/- 126.8 mumol/l in RA patients without iron deficiency (n = 72) and 267.9 +/- 148.4 mumol/l in RA patients with iron deficiency (n - 43), which were significantly higher than those of healthy controls (32.7 +/- 14.3 mumol/l, p < 0.01, respectively). There were no significant differences in mean NOx concentrations between the patients with CRP < 0.7 mg/dl and with CRP greater than or equal to 3.0 mg/dl, nor between the patients with ESR < 15.0 mm/h and with ESR greater than or equal to 40.0 mm/h. Serum NOx concentrations showed no significant correlations with CRP, ESR, and RF but exhibited an inverse correlation with serum iron markers. Conclusion: NO production markedly increases in patients with RA, however, serum NOx concentration does not seem to be associated with disease activity of RA, at least on the basis of laboratory data of CRP, ESR, and RE (C) 2003 Elsevier B.V. All rights reserved.