The cytoprotective effects of liquid sucralfate and a synthetic analog of prostaglandin E1 (PGE1) on acid-induced esophagitis in cats were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N HCl at 1 ml/min for 20 min. Animals were infused for either one or three days. Mucosal lesions were evaluated by blinded investigators using both fiberoptic endoscopy and light microscopy. Histologic changes included basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions in both one- and three-day infusions, demonstrated by both endoscopy and quantitative histologic scoring. Indomethacin (200 micrograms/kg) given prior to sucralfate and acid did not affect sucralfate cytoprotection. Synthetic PGE1, given in doses of 5 micrograms/kg and 100 micrograms/kg, afforded no esophageal cytoprotection. These studies indicate that sucralfate is cytoprotective against acid-induced esophageal injury in cats, an effect that does not appear to be mediated by prostaglandin. In addition, synthetic PGE1 does not confer protection in this animal model.