1. The antiulcerogenic effects of cisapride, a potent benzamide-stimulating gastrointestinal motility agent, were studied on cold-resistant and pylorus-ligated gastric ulcers. Acidity, composition of gastric secretion, and quantitative and qualitative changes on mucus glycoprotein content were also determined. These effects were compared with those of ranitidine (50 mg/kg) and omeprazol (10 mg/kg). 2. Oral cisapride (10-100 mg/kg) dose-relatedly and significantly (P < 0.01, P < 0.05) decreased the severity of the lesions induced by cold-resistant stress. In stressed rats, cisapride increased the amount of mucus secretion and markedly enhanced the glycoprotein content. Morphometric evaluation of mucus secretion revealed a significant increase in both the PAS area (neutral glycoproteins) and Alcian blue area (sulfated glycoproteins). 3. In 4 h pyloric-ligated animals, cisapride (10-100 mg/kg) showed a significant reduction in the number and severity of ulcers (P < 0.01) and histamine concentration (P < 0.01, P < 0.001). In addition, at the highest doses (50-100 mg/kg), cisapride produced a significant decreases in acidity; however, it did not alter the gastric volume secretion or pepsin concentrations. 4. These results suggest that cisapride shows antiulcerogenic effects which could possibly be explained through antisecretory and cytoprotective mechanisms involving an enhancement of cuality and production of gastric mucus.