Several high molecular weight proteins were observed in dissociative extracts of osteoarthritic, but not of normal, human cartilage. By gel electrophoresis, by DEAE-cellulose and gelatin-agarose chromatography, and immunologically, they were found to be identical to fibronectin. Incorporation of tritiated proline into these proteins indicated that this material was not a synovial fluid contaminant. Interactions with the proteoglycans suggested that, in articular cartilage, the role of fibronectin may be more closely associated with proteoglycans than with collagen. The appearance of fibronectin in the diseased cartilage suggests that this may be a feature of the chondrocyte's repair response to the loss of extracellular matrix.