We report the use of immunologic methods for detecting specific alterations in human osteoarthritic cartilage. Monoclonal antibodies with specificities for proteoglycans and link proteins have been used to define immunogenic sites in these molecules. We have identified 1 site in the protein core, 1 site in the link proteins, and another site that is common to both proteoglycan and link proteins, which are not modified in osteoarthritic cartilage. In addition, an antigenic determinant in link proteins that is altered in osteoarthritic cartilage has been identified. These results suggest that the structure of the ternary complex (hyaluronic acid binding region-link proteins-hyaluronic acid) could be altered in osteoarthritic cartilage. These modifications may be due to a genetic defect or to partial enzymatic degradation of these sites.