Mice that lack the ability to produce gastrin (Gas-KO) are unable to secrete .gastric acid in response to acute stimulation by the appropriate secretagogues. It is thought that this is due to the presence of immature parietal cells that lack the ability to secrete acid, although it'is possible that the secretion of acid is chronically inhibited in the absence of gastrin. Treatment of these mice with gastrin restores the ability of the parietal cells for gastric acid secretion indicating that gastrin is required either for the maturation of parietal cells or to remove the inhibition of acid secretion. Ezrin, a cytoskeletal-membrane linker protein required for gastric acid secretion, has previously been shown to be decreased in the stomachs of Gas-KO mice compared to wild type mice, and to be increased following gastrin treatment. In this study it is shown that the expression of ezrin is significantly decreased in the parietal cells of Gas-KO mice and is increased following treatment with gastrin. It is also shown that the expression of COX2 is significantly increased in the stomachs of Gas-KO mice, indicating that the secretion of gastric acid might be inhibited by prostanoids synthesised as a result of increased COX-2; the expression of COX-2 in the parietal cells of Gas-KO mice is decreased by treatment with gastrin. Treatment of Gas-KO mice with a COX-2 inhibitor decreases the intragastric pH of these mice, as well as increasing the expression of ezrin in the parietal cells, implying that the expression of ezrin in parietal cells might be regulated by gastrin via suppression of COX-2. It is also shown that the number of a subepithelial cell type, the myofibroblast, is increased in the stomachs of Gas-KO mice, and that the inhibition of COX-2 decreases the number of myofibroblasts. It is apparent that the loss of gastrin therefore has consequences, not only for the function of parietal cells and the gastric glands but also the architecture of the stomach outside of the gastric epithelium.