We studied the background gastric mucosa in eight patients with intractable peptic ulcer in whom gastric cancer developed during more than 4 years' administration of histamine (H)2-receptor antagonists (H2-RAs), and in two patients with intractable gastric ulcer without gastric cancer in whom H2-RAs were administered for 4 years. As controls, we studied background mucosa in seven patients with combined gastroduoderal ulcers not treated with H2-RAs. The cancers were differentiated adenocarcinomas in all eight patients. The characteristic features of these patients and of the two patients with intractable gastric ulcer were: expansion of the generative cell zone, poor differentiation of the goblet cells, mild cellular atypia, and abnormal branching and anastomosis of glands, as well as wide areas of incomplete-type intestinal metaplasia. The sites of the differentiated adenocarcinomas were classified by mucin histochemistry as intestinal-type mucosa in all patients. A special type of incomplete intestinal metaplasia, of the intestinal type and which retained gastric-type properties, was present in some areas, and p53-positive cells were observed in some areas. In patients with intractable gastric ulcer in whom the background gastric mucosa had been exposed to more than 4 years of H2-RA treatment, it was considered possible that the preconditions for cancerous lesions were present.