It is known, that plasmin is capable of specifically activating the complement factors C1 q and C3. In addition plasmin can activate procollagenase to collagenase. Since both mechanisms could possibly play a decisive role in the pathogenesis of rheumatoid arthritis, we have carried out animal experiments to investigate the primary role of plasmin in the development of arthritis. Twenty-two rabbits were subjected to intraarticular injection with an equal dose of plasmin on days 1, 4, and 8. An aspirate was taken on day 9 for a white cell count and a histological investigation of the synovial tissue. Already after a single dose of 0.25 CU plasmin an inflammatory reaction was clearly observed. Increasing amounts of plasmin (2.5 and 12.5 CU) caused an increased inflammatory response. On the basis of these results, it is discussed whether the observed arthritic reaction after plasmin injection is caused by complement activation. Possible analogies with rheumatoid arthritis are discussed.