1 Since nonsteroidal anti-in¯ammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. 2 Explants were sampled from the medial femoral condyle and were classi®ed by use of the Mankin's histological-histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3 Cartilage explants were pulsed with [-3H]-glucosamine and chased in the absence or in the presence of 0.3 ± 3 mg ml 71 of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and media were puri®ed by anion-exchange chromatography. 4 In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaected by diclofenac. In contrast, and in a dose-dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced signi®cantly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from cartilage explants. 5 The data obtained in short-term in vitro cultures indicate that, at the concentrations found in synovial¯uid, aceclofenac and meloxicam may exert a favourable eect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.