We have used an ELISA to quantify a highly sulfated epitope present on keratan sulfate, a carbohydrate chain found principally in cartilage proteoglycans. The serum level of the epitope provides an indirect measure of the rate of degradation of cartilage proteoglycans during normal turnover and can be used to diagnose specific abnormalities in keratan sulfate metabolism. Serum levels of the epitope are elevated in a high percentage of patients with osteoarthritis and correlate with the number of joints involved. The elevated rate of proteoglycan turnover in these patients appears to be systemic, affecting not only the degenerating articular surfaces but apparently normal articular cartilages as well. We have postulated that this acceleration in the rate of proteoglycan turnover precedes clinical evidence of degenerative changes; and we discuss the rationale for the contention that this elevation may predispose adult humans to polyarticular osteoarthritis.