The role of platelet-activating factor (PAF) in mediating the colonic damage that develops after large-colon torsion was studied in 14 ponies. Morphologic changes in areas of the ascending colon and selected abdominal and thoracic viscera after 1 hour of large-colon torsion and 3 to 5 hours of reperfusion were determined, as well as the protective effects of systemic administration of a specific PAF antagonist (WEB 2086). Ponies were selected then allocated at random and in equal numbers to 2 groups that received 1 of 2 treatments prior to induction of large-colon torsion: group 1 - control (saline solution), and group 2 WEB 2086 (3 mg/kg of body weight loading dose and 3 mg/kg/h for the remainder of the study). In each pony, full-thickness tissue specimens from the gastrointestinal tract-cecum, pelvic flexure, left and right ventral colon, and right dorsal colon - heart, left lung, liver, left adrenal gland, spleen, and right kidney were collected and histologically evaluated. Edema, mucosal necrosis, and neutrophil infiltration in colonic sections were graded from 0 (normal) to 3 (most severe changes). Sections of liver and lung from 3 ponies in each group, and colon from 1 pony in each group, also were examined by transmission electron microscopy to determine the presence of ultrastructural alterations. Ischemia and reperfusion induced marked changes in all sections of colon in all ponies: moderate to severe submucosal edema, moderate necrosis of the superficial epithelium and lamina propria, and necrosis of the mucosal crypt epithelium. Extra- vascular neutrophil accumulation was evident in all sections of colon and cecum, but not in other tissues. Ultrastructural lesions were not present in hepato- cytes or pneumocytes, or in the endothelial cells of liver, lung, and colon. Bacteria were observed by electron microscopy in 5% of hepatic sinusoids. Administration of a specific PAF antagonist, WEB 2086, failed to reduce severity of the observed lesions, indicating that it was not cytoprotective at the dosage used in this model of ischemia-reperfusion injury.