Rats were tube-fed with omeprazole (40 μmol/kg body weight twice daily) for 30 and 60 days. As a result, fasting plasma gastrin levels were significantly elevated, while plasma somatostatin levels remained normal. Gastrin concentrations in the antral mucosa were unchanged after 30 days, but significantly elevated after 60 days. The relative stomach weight and the area of the antral and oxyntic mucosa increased significantly; however, the oxyntic mucosa thickness and the volume density of the parietal cells did not increase. Highly significant changes occurred in the endocrine cells of the antrum and corpus. The volume density of the argyrophilic (Grimelius technique) cells of the oxyntic mucosa increased time-dependently, and so did the volume density of the antral G cells, while the volume density of the antral D cells decreased. This resulted in a remarkable increase in the G/D cell ratio. All functional and morphological changes are reversed 42 days after omeprazole feeding for 60 days. The findings in the endocrine cells of the antral mucosa are explained by the omeprazole-induced permanent elevation of the intragastric pH and in the endocrine cells of the oxyntic mucosa by the following hypergastrinaemia.