The polyamines spermidine and spermine are essential for cell proliferation. Most growth factors stimulate polyamine synthesis by inducing ornithine decarboxylase activity, which catalyzes the formation of putrescine from ornithine. Putrescine can then be utilized either for polyamine biosynthesis or may serve as a substrate for diamine oxidase (DAO), leading to formation of gamma-aminobutyric acid (GABA). Growth of the oxyntic mucosa of the stomach is stimulated by feeding, by trophic hormones such as gastrin and by exogenous administration of putrescine. Conversely, fasting, as well as ornithine decarboxylase inhibition decrease oxyntic mucosal DNA synthesis. We now demonstrate that fasted rats show a high degree of [3H]GABA formation from [3H]putrescine in the oxyntic mucosa and that feeding or injections of gastrin, caerulein or the DAO-inhibitor aminoguanidine decrease such [3H]GABA formation and, instead, stimulate formation of [3H]spermidine. Moreover, gastrin injections reduced oxyntic mucosal DAO activity. Thus, oxyntic mucosal DAO activity is regulated by tropic factors and may be involved in growth regulation by controlling intramucosal putrescine metabolism.