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The effect of a series of six spaced injections of papain administered into the eblow joints of thirty adult rabbits over a twelve-day period was studied by clinical, roentgenographic, and histological means. Animals were sacrificed two, four, and six weeks after the start of the experiment. A marked chondrolytic effect associated with signs of acute arthritis was noted. Almost all the articular cartilage showed signs of erosion. About 75 per cent of the articular surface was reduced to a basal layer of cartilage several cells in height. A marked periarticular inflammatory reaction developed, with thickening of the capsule, periosteal new-bone formation, and patchy covering of the eroded articular surface with a fibrocartilaginous callus.Twenty-seven rabbits received a series of six papain injections into the elbow joint and later were operated on to immobilize the elbow by extra-articular stapling. A 0.5-centimeter segment of the upper part of the humeral shaft was resected and the nerves to the triceps were divided in the same limb. At autopsy, eight weeks later, osseous ankylosis of the elbow was established in eighteen animals (67 per cent). Fusion did not occur in any of fourteen animals receiving identical treatment using an enzyme inactivated by boiling. Surgical arthrodesis using intra-articular autogenous bone grafts and the same immobilization technique produced fusion in seven of ten animals.