The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.