Interleukin-6 (IL-6) was detected at low levels in plasma [0.014 +/- 0.006 ng/ml (mean +/- SEM] and in high amounts in synovial fluid [SF; 2.6 +/- 2.2 ng/ml (mean +/- SEM)] of patients with rheumatoid arthritis. No correlation of IL-6 levels in plasma or SF with the ESR (n = 15) or with histological parameters of acute local synovitis (n = 10) was observed. In contrast, SF IL-6 was positively correlated with histological characteristics of chronic synovitis (n = 10; P < or = 0.01) and elevated plasma IgG concentrations (n = 15; P < or = 0.05). In vitro concentrations of IL-6 comparable to those detected in SF increased the production of both IgG and IgM by synovial membrane mononuclear cells. The present results contribute to the view that high local IL-6 concentrations in SF promote chronic synovitis in RA.