The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.