We determined the degradation of articular cartilage proteoglycans in a single episode of experimental hemarthrosis in rat knees. The right knee joints of rats were injected once with autologous whole blood. Both knee joints were examined histologically. Biochemical studies of cartilage proteoglycans extracted from the knees were also conducted. Histological examination revealed an accumulation of mononuclear cells in intraarticular fibrin clots and subsynovial layers 8 hours after the injection of blood. Accordingly, initiation of proteoglycan degradation occurred 8 hours after injection of blood, lasting from 1 day of limited degradation to 3 days; recovery then occurred within 7 days. The proteoglycan degradation could be inhibited by 1 mM phenylmethylsulfonyl fluoride, a general serine proteinase inhibitor, 0.1 M 6-aminohexanoic acid, a specific inhibitor of plasminogen activators, 10 mM EDTA, and 10(-6) to 10(-8) M dexamethasone, indicating that the accumulation of mononuclear cells in intraarticular fibrin clots and subsynovial layers may play an important role in cartilage damage.