Postsurgical adhesions represent a common complication following a variety of surgical procedures. We sought to develop and evaluate a water-soluble polymer that could self-assemble onto tissue surfaces, forming a barrier on the surface. A copolymer was synthesized so as to contain two components: one component adsorbed to the tissue surface, and the other created a steric barrier, thereby preventing cell interactions with the tissue surface, and perhaps altering the wound-healing response that leads to the formation of fibrous adhesions. The component selected for tissue binding was a water-soluble polycation, poly-L-lysine, which can bind to negative sites on glycoproteins, proteoglycans, and cells; and the component selected for steric stabilization was polyethylene glycol, a nonionic polymer that interacts poorly with proteins. Efficacy of lavage with an aqueous solution of the copolymer for the prevention of postsurgical abdominopelvic adhesions was assessed following a standard electrocautery injury of the uterine horns of rats. The copolymer resulted in an 88% reduction in the extent of adhesions that formed. In vitro studies designed to investigate the mechanism of this efficacy indicated that the copolymer may both hinder cell-tissue adhesive interactions and alter the process of fibrin formation. [on SciFinder (R)]