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Pentosan polysulphate (PPS) and glycosaminoglycan polysulphate (GAGPS) were examined for their ability to alter hyaluronan synthesis in vivo. The inflamed rat subcutaneous air pouch model was used for the study. PPS or GAGPS injected into the air pouch at a dose of 2.5 mg/kg daily for 7 days resulted in higher molecular weight hyaluronan in the pouch fluid compared with control non-drug-treated pouch fluid. The quantity of the hyaluronan was increased by PPS, but not by GAGPS. We concluded that both drugs could be beneficial in the treatment of inflammatory arthritides in which a decrease in normal synovial hyaluronan concentration and molecular weight occurs.