We examined the relationship between collagenase activity and the clinical course of the patients with rheumatoid arthritis (RA). The activity of active and inactive collagenase (treated by 3M-KI) was assayed several times for synovial fluid from twelve RA patients and one patient with osteoarthritis (OA). Rheumatoid factor, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leukocyte counts and acid-phosphatase activity in the synovial fluid were measured simultaneously. In seven of twelve cases, the change of inactive collagenase activity was parallel by changes in synovial leukocyte counts or acid-phosphatase activity. In five of seven cases, the change in inactive collagenase activity was paralleled by acid-phosphatase activity and leukocyte counts. These findings suggest that collagenase activity is intimately correlated with the grade of local inflammation of RA and that the change of collagenase activity is closely correlated with the clinical course of RA patients.