Hypertrophic gastritis, histologically characterized by a depletion of parietal and chief cells and by varying degrees of lymphocyte infiltration along the thickened muscularis mucosa, could be induced by neonatal thymectomy (Tx) without any additional treatment in about 50% of mice (C3H/HeMs X 129/J)F1 (C3.129). The thickness of the mucosa in gastritic mice increased with age, forming giant folds. In Tx mice with an early stage of abnormal mucosal folds at 6 months of age, numbers of parietal cells per mucosal tissue unit area (parietal cell densities) and ratios of parietal cells to mucous cells became lower than in control mice, and serum gastrin levels became contrastingly higher with the increasing severity of gastritis. Circulating antibodies against parietal cells (APA) were detected by indirect immunofluorescence (IFL) in the mice. A good correlation was observed between APA and gastritis: APA with high titers (more than 1,000-fold dilutions) appeared when severe lesions were found. In mice with giant mucosal folds at 18 months of age, serum protein levels were within normal limits, but fecal clearance rates of 125I-labelled polyvinylpyrrolidone (125I-PVP) were significantly increased. These results suggest that the hypertrophic gastritis induced by neonatal Tx is characterized by hypergastrinemia due to parietal cell depletion caused by the presence of circulating APA and the protein loss from the hypertrophic mucosa. Both histological and physiopathological similarities were found between the gastritis in the mice and Menetrier's disease in man.