Anti-arthritic action of superoxide dismutase (SOD) was studied in rabbits. Arthritis was induced by intraarticular injections of lambda-carrageenin (1%, 1 ml) into the knee joint weekly for two weeks. In this experimental arthritis, acid phosphatase activity, quantities of protein, uronic acid and lipid peroxide, and leukocyte counts in the synovial fluid increased; and the quantity of uronic acid in the articular cartilage decreased. Microscopic findings of the synovial membrane showed a proliferative synovitis. The responses of the left and right knee joint to carrageenin were much to the same in degree, so that the anti-arthritic action of SOD by intraarticular injections was evaluated on one knee joint, referring to the other joint as a control (saline injections). Two injections of SOD (350 SOD unit = 0.1 mg), one a week, suppressed the inflammatory changes in the biochemical parameters of the synovial fluid and the articular cartilage; particularly, significant inhibitory effects on acid phosphatase, lipid peroxide and leukocyte were observed. The microscopic findings of the synovial membrane also revealed that SOD was efficacious. On the other hand, 0.1 mg of denatured SOD, prepared by reducing the S-S bond or heating under an alkaline condition, did not show any anti-arthritic activity. These results suggest that the anti-arthritic action of SOD actually depends on the enzymatic activity of superoxide dismutase.