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The ideal contrast agent in patients suspected of having gastrointestinal perforation is an iso-osmolar, or nearly iso-osmolar substance, that causes no peritoneal reaction. Iopamidol is a nonionic water-soluble contrast medium that may be considered in such situations. Intraperitoneal injections of ionic and nonionic contrast agents were compared in rats to study potentially harmful peritoneal inflammation. Only intraperitoneal barium injection produced any significant tissue reaction, such as adhesions and ascites. There was no difference between iopamidol and the other water-soluble contrast agents. Iopamidol may satisfy the need for nonreactive and nearly iso-osmolar contrast agents for evaluating patients with possible bowel perforation. However, the high cost of this agent may make its clinical application impractical.