To define autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis, extracts were obtained from articular cartilage specimens from 16 patients with rheumatoid arthritis, 11 patients with osteoarthritis, and 6 normal controls. Radioimmunoassays of the extracts revealed that rheumatoid cartilage contained 37 times more IgM and 14 times more IgG than did normal cartilage extracts. In addition, osteoarthritic cartilage contained 3 times more IgM and IgG than the normal tissues. IgM rheumatoid factor was found in 13 of 16 rheumatoid cartilage extracts but in none of 11 osteoarthritic or 6 normal control extracts. IgG rheumatoid factor was detected in 4 of 7 seropositive rheumatoid but in none of 5 osteoarthritic cartilage extracts. More than 60% of the rheumatoid cartilage extracts were positive for native and denatured collagen I1 antibodies. Surprisingly, 50% of the osteoarthritic specimens also contained significant titers of collagen antibodies. Similar results were obtained with osteoarthritic menisci extracts. These findings indicate that the immune complexes sequestered in rheumatoid cartilage contain autoantibodies that are probably synthesized locally by cells infiltrating the inflamed synovium. If immune complexes trapped in cartilage play an important role in cartilage damage, our findings would provide a possible pathogenic mechanism that explains the self-perpetuating and chronic nature of cartilage degradation in rheumatoid arthritis and osteoarthritis.The pathophysiologic mechanisms operative in articular cartilage damage in rheumatoid arthritis (RA) are not completely understood. However, the pathologic changes observed in advanced disease indicate that most of the cartilage erosive lesions are associated with the invasion of the articular and deep areas of cartilage by pannus originating from the inflamed synovium (1,2). Although the conditions that initiate and facilitate pannus invasion are unknown, previous work in our laboratory suggested that sequestered immune complexes commonly found in the superficial areas of rheumatoid cartilage (3) may play a role in the destructive process by inducing pannus invasion (4) or by activation of the resident mononuclear phagocytes within this granulation tissue (5,6). Rheumatoid synovial fluids frequently contain large amounts of immunoglobulin with autoantibody specificities, synthesized in part by plasma cells infiltrating the subsynovial membrane (7,8). Thus, it was of particular interest to define the possible autoantibody specificities of immune complexes sequestered in articular cartilage. Our findings indicate that rheumatoid factor (RF) and/or collagen antibodies are found in the majority of cartilage tissue specimens obtained from joints of patients with advanced RA. Surprisingly, more than 50% of specimens from patients with osteoarthritis (OA) also contained collagen antibodies. These findings may provide an explanation for the self-perpetuating and chronic nature of ...