The cytokine interleukin-1 plays an important role in the production and modulation of the immune response in rheumatoid arthritis. It is produced by macrophages of the inflamed synovial tissue and induces the autocrine production of interleukin-1, amplifies the T-cell dependent immune response and has potent effects on inflammatory reactions of many non-lymphoid cell-systems. By means of a sensitive and specific ELISA interleukin(Il)-1 beta was measured in the peripheral blood and synovial fluid of patients with rheumatoid arthritis in comparison to controls in significantly increased levels (medium values: 280 pg/ml and 325 pg/ml versus less than 20 pg/ml). The Il-1 beta concentrations in the peripheral blood and in the synovial fluid were well correlated, but there was no correlation to other inflammation parameters like erythrocyte sedimentation rate or C-reactive protein, however, a good correlation to the nephelometrically measured rheumatoid factor (r = 0.71). In twelve hour cultures of adherent cells significantly increased spontaneous intracellular Il-1 beta-production was determined in synovial fluid macrophage cultures of rheumatoid arthritis patients compared to peripheral blood monocyte cultures of controls (median values 91.0 ng/10(6) cells versus 31.5 ng/10(6) cells). The secretion into the culture supernatant has to be stimulated by additional lipopolysaccharide. Interferon-gamma inhibits the spontaneous intracellular Il-1 beta-production of synovial fluid macrophages from rheumatoid arthritis patients. These findings may be of importance for the effect of the interferon-gamma therapy in the treatment of rheumatoid arthritis.