Abstract In Lai-rats gastric mucosal histamine and histidine decarboxylase were estimated after stimulation of gastric acid secretion by intravenous infusions of submaximal doses of pentagastrin for 1 or 2 h. Pentagastrin produced a dose-dependent acid response with a maximum of 26 μ equiv H+ per 10 min at a dose of 2.56 μg kg−1 min−1. There was a linear relation between the log dose of pentagastrin and the activation of gastric histidine decarboxylase. The highest dose of pentagastrin yielded a histidine decarboxylase activity of 200% of the unstimulated level when infused for 1 h and of 290% when infused for 2 h. No reduction of gastric mucosal histamine could be detected whatever the dose of pentagastrin or the duration of infusion. It was concluded (1) that stimulation of gastric histidine decarboxylase is a physiological function of gastrin-like peptides, (2) that a reduction of gastric mucosal histamine by gastrin or pentagastrin is a pharmacological rather than a physiological effect, and (3) that no negative feedback relation exists beween gastric mucosal histamine and the activation of histidine decarboxylase.