New developments in the study of the pathogenesis of experimental gastric and duodenal ulcers indicate a complex multifactorial process leading to ulceration. The concept of gastric cytoprotection with prevention of hemorrhagic mucosal lesions by PG, SH, or other compounds without inhibiting acid secretion was discovered while investigating animal models of gastric erosions and ulcers. Subsequent research into the pathophysiology of gastric ulcer has been revitalized. New studies have demonstrated that the development or prevention of vascular injury in the gastric mucosa plays a crucial role in gastric mucosal injury and protection. The pathophysiology of experimental duodenal ulcer disease has shown that controlling gastric acid secretion is not the only approach to the prevention or treatment of this disorder. Data from human and animal experiments suggest that duodenal dysmotility contributes to the decreased neutralization of acid whether secreted at a normal or subnormal rate, in the duodenal bulb. Dopamine infusion corrected experimentally induced duodenal hypermotility, but other neurotransmitters may also be involved. Multidisciplinary investigations using experimental models of gastric and duodenal ulcers lead not only to the discovery of new concepts and pathogenetic mechanisms but also to the recognition of new chemicals that may exert gastroprotective and antiulcerogenic effects.