The aim is to study the protective effects of topical sucralfate and geraniin on acidified ethanol (EtOH dissolved in 100 mM HCI plus 54 mM NaCl)-induced gastric acid back-diffusion, mucus production and mucosal ulcerations in the rat. After irrigation the stomach with acidified EtOH (10-40% v/v) for 3 hrs, a concentration-dependent increase in acid back-diffusion and in mucosal lesions, and -dependent reduction in mucus production was found. These ulcerogenic effects of EtOH were dose-relatedly inhibited by pretreatment of intragastric sucralfate (10-200 mg/kg). A high correlation (r = -0.9572) between sucralfate-induced inhibition in acid back-diffusion and -induced reduction in mucosal ulceration provoked by 30% EtOH was observed. Geraniin (10-100 mg/kg), given 30 min prior to EtOH perfusion, produced potent inhibitory effects on those ulcerogenic parameters provoked by EtOH in a dose-dependent manner. The correlation (r = -0.8638) between geraniin-induced inhibitions in acid back-diffusion and in mucosal ulceration produced by EtOH was achieved. These cytoprotective effects of sucralfate and geraniin were further confirmed by morphological and histological studies. The results suggested that the protective effects of sucralfate and geraniin on gastric mucosa against acidified EtOH-induced damage are at least partly through the inhibition in acid back-diffusion and the elevation of gastric mucus production.