Growing evidence suggests that biochemical mechanisms play a role in the pathogenesis of arthritis. Cartilaginous wear particles have been shown to induce destructive enzymes and cytokines. To assess the biocompatibility of artificial ACL replacements, the effects of wear particles from the following ligaments were analyzed biochemically and histologically: GORETEX, Stryker Dacron Ligament Prosthesis, Versigraft carbon, Kennedy LAD, Xenograft, Leeds-Keio, and human patellar tendon allograft. Ligaments were frozen and ground to produce wear particles similar to those seen clinically and were added to lapine synovial cell cultures. The resulting conditioned medium was analyzed for collagenase, gelatinase, and chondrocyte activating factor (CAF) production. All of the ligaments induced significantly elevated enzyme and CAF production by the synoviocytes, with Xenograft and carbon inducing significantly higher enzyme levels than those of the other five ligaments. Five milligrams of wear particles were injected into the knees of 4 kg to 5 kg rabbits that were analyzed histologically after 14 weeks. Wear particles accumulated in the periarticular synovial folds and induced modest to severe macrophage infiltration in the synovium. A hypothetical model explaining the role of artificial ligament wear particles in the pathogenesis of arthritis is presented.