Adhesion formation after peritoneal surgery is a major source of postoperative complications and pain. Previous studies showed that intraperitoneal administration of the nonsteroidal anti-inflammatory drug tolmetin reduced adhesion formation after two types of peritoneal surgery. The effect of tolmetin combined with hyaluronic acid (HA), a high-molecular-weight glucosaminoglycan found in the extracellular matrix, on the formation of adhesions was examined. In this study, the effect of tolmetin in HA on adhesion formation was evaluated in a standardized rabbit model. The medicament was administered intraperitoneally at the end of surgery. One week after surgery, a second laparotomy was performed and the extent of adhesion formation was determined. A range of molecular weights (7.5 x 10(5)-2 x 10(6) Da) and viscosities (1000-25,000 centapoise) of HA in combination with tolmetin was effective in reducing adhesion formation. However, low viscosity HA solutions in combination with tolmetin, 0.5-2.0 mg/mL, were most efficacious in reducing adhesion formation. These data suggest that HA, in combination with tolmetin, acts as an effective carrier to reduce adhesion formation in the abdominal cavity after surgery.