In order to investigate the possible role of IL-1 receptor antagonist (IL-lra) in patients with rheumatoid arthritis (RA), this study was undertaken to measure the amounts of IL-lra and interleukin-1β (IL-1β) protein produced by mononuclear cells (MNC) and to investigate the relationship between production of these cytokines and clinical parameters. The MNC were cultured for 24 h and the supernatants were measured for IL-lra and IL-1β by ELISA kits. MNC from peripheral blood (PB) and synovial fluid of RA patients produced significantly higher amounts of IL-lra than normal PBMNC (P < 0.01 and P < 0.05, respectively). When the IL-1β/IL-lra ratio was calculated, IL-1β/IL-lra ratios of RA PBMNC were significantly lower than those of normal PBMNC (P < 0.001). The IL-1β/IL-lra ratio of RA PBMNC was significantly higher in active RA patients than in RA patients in remission (P < 0.02). The amounts of IL-lra produced by stimulated RA PBMNC positively correlated with the joint score (P < 0.05), serum CRP levels (P < 0.05) and the amounts of IL-1β produced (P < 0.01). The amounts of IL-lra produced by unstimulated RA PBMNC did not correlate with any of the clinical parameters studied. Gold sodium thiomalate (GST), but not auranofin, increased IL-lra production in vitro. These data suggest that increased IL-lra production in RA MNC is associated with IL-1β produced, thus protecting from IL-1β-mediated immune responses, and that enhanced IL-lra production by MNC cultured with GST is one of the mechanisms by which GST shows clinical efficacy.