We examined the activities of peptidases in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase IV (DPP IV) activity was lower in synovial fluid from patients with RA, in contrast to the increase of DPP II activity in synovial fluid, as compared with OA. The DPP II/DPP IV ratio for synovial fluid was significantly higher in patients with RA than in patients with OA. A significant correlation was observed between the DPP II/DPP IV ratio for synovial fluid from patients with RA and the amount of C-reactive protein reaction. These results may be useful in the diagnosis of joint effusion of unknown origin.