Human synovial fluid often contains small cartilaginous "wear particles." Previous in vitro experiments have indicated the potential involvement of these particles in the pathophysiology of arthritis. To determine whether this potential is realized under the conditions existing within joints, standard suspensions of lapine articular cartilage were injected intraarticularly into the knee joints of rabbits. Thrice-weekly injections of 1 mg allogenic cartilage produced an inflammatory arthritis, accompanied by a marked cellular effusion, in all rabbits within 5 months. The synovium became hyperplastic, discolored, and infiltrated with mononuclear inflammatory cells. Embedded particles of the injected material were seen in histologic preparations of these synovia. Organ cultures of such synovia produced 4 to 5 times more collagenase, plasminogen activator, "Pz-peptidase," neutral and acid azocaseinase, and beta-glucuronidase than did cultures of synovia from control knees injected with saline. Furthermore, the articular cartilage of knees injected with cartilaginous particles showed elevated intrinsic collagenolytic activity. Histologic examination of the articular cartilage revealed an attendant loss of metachromasy, resulting in friability, pitting, and discoloring of the cartilage. Preliminary immunoassays failed to demonstrate a systemic immune response to the injected material.