Rheumatoid arthritis (RA) is a systemic disease characterized by chronic inflammation of synovial joints accompanied by a marked acute phase response, and interleukin-6 (IL-6) is a major mediator of the inflammatory response which is involved in the induction of acute phase protein, To evaluate the significance of IL-6 levels in patients with RA, IL-6 activity was measured by radioimmunoassay in 13 patients with RA and 5 patients with traumatic arthritis (TA) or osteoarthritis (OA) was used as a control group. Serum IL-6 activity was significantly elevated in 2 RA patients without treatment compared with that of 11 RA patients with treatment and all the TA and OA patients. Synovial fluid IL-6 activity was elevated in all RA patients (markedly elevated in 2 RA patients without treatment) compared with that of TA and OA patients. Immunohistochemical analysis of synovial tissue from 3 RA patients revealed strong expression of IL-6 in most inflammatory synovial cells. The results indicate that IL-6 level, especially that of synovial fluid, is related to disease activity in patients with RA.