Cartilage contains a number of matrix macromolecules not present in other connective tissues. In tissue processes in disease and in normal turnover of the matrix these molecules are fragmented and released into surrounding fluids, in the case of joints into the synovial fluid. Immunoassay techniques have been developed to quantify these fragments. It appears that increased levels in synovial fluid (SF) correlate to a process in the joint cartilage. With successful therapy the level returns to normal. Interestingly, in early rheumatoid arthritis, i.e., with no discernible cartilage damage by radiography, a high SF level of one major cartilage component (proteoglycan aggrecan/fragments) is prognostic for future extensive cartilage destruction. There are major differences in the levels of proteoglycan fragments between different disease groups. Thus, patients with acute reactive arthritis have high SF levels, while patients with late rheumatoid arthritis with extensive cartilage destruction not surprisingly have subnormal values. Patients with osteoarthritis, even those with fairly extensive cartilage destruction, have elevated levels of proteoglycans/fragments in their SF, perhaps indicative of a more pronounced reparative phase.