A specific gastritis was induced in BALC/c (+/?) mice by thymectomy within 3 days after birth (25 to 45 per cent) or in BALB/c (nu/nu) mice by the injection of spleen cells (10(7)) from neonatally thymectomized mice (70 per cent). Normal peripheral lymphoid cells, irrespective of the sex and dose, were generally ineffective in inducing gastritis in nude mice, while thymus cells were partially effective (30 per cent). The induced gastritis was characterized by a loss of chief and parietal cells and by varying degrees of lymphoid cell infiltration along thickened muscularis mucosa. The fundic mucosa was replaced by mucous necklike immature cells, and there was a rise of pH of the gastric juice. Argyrophilic endocrine cells escaped the inflammation and increased in number. The gastritis induced in nude mice was generally more severe and was often followed by severe macrocytic anemia. Megaloblast-like large immature erythroid cells were numerous in the spleens of affected mice. Antiparietal cell antibodies (IgG) were always demonstrated by an indirect immunofluorescence test in the sera of gastritis-developing mice, but were absent in sera of normal or untreated conventional nude mice. These findings suggest a new animal model of pernicious anemia in man.