The incidence, number, and histological types of gastric cancers induced by N-methyl-N′-nitro-N-nitrosoguanidine and the tissue norepinephrine concentration of the gastric wall were investigated in spontaneously hypertensive rats and in control Wistar Kyoto rats and Wistar rats. All rats were given drinking water containing 25 µg/ml of N-methyl-N′-nitro-N-nitrosoguanidine for 25 weeks. During Week 52, the incidence and number per rat of gastric cancers were significantly greater in spontaneously hypertensive rats than in Wistar Kyoto and Wistar rats. All tumors induced in the glandular stomach were adenocarcinomas, but no significant difference was found in the histological types of adenocarcinoma in the three strains of rats. At Weeks 15, 30, and 52, norepinephrine concentrations in the fundic and antral portion of the gastric walls and labeling indices in the antral and fundic mucosa were significantly higher in spontaneously hypertensive rats than in Wistar Kyoto and/or Wistar rats. These findings indicate that increased sympathetic nervous system activity enhances the development of gastric cancers, but immunological dysfunction in spontaneously hypertensive rats may contribute to the increased susceptibility to gastric cancer.