Twenty-four young adult domestic cats from a commercial vendor were found to be infected with Helicobacter pylori. Histopathologic analyses, selected electron microscopy, and urease mapping were performed on mucosal samples collected from the cardias and fundi, bodies, and antra of these cats' stomachs. H. pylori organisms were abundant in all areas of the stomach on the basis of histologic evaluation and urease mapping. H. pylori infection was associated with a moderate to severe lymphofollicular gastritis in 21 of 24 cats (88%). The gastritis was most pronounced in the antral region and consisted mainly of multifocal lymphoplasmacytic follicular infiltrates in the deep mucosa. The severity of gastritis in the antrum corresponded to high numbers of H. pylori there on the basis of the use of the urease assay as an indicator of H. pylori colonization. Ten of 24 cats (42%) also had small to moderate numbers of eosinophils in the gastric mucosa. All 24 cats had gastric lymphoid follicles, with follicles being most prevalent in the antrum. Electron microscopy of gastric tissue revealed numerous H. pylori organisms, some of which were closely adhered to the mucosal epithelium. Human H. pylori gene-specific primers to ureA and ureB amplified products of similar sizes from H. pylori cat isolates. Digestion of the products with restriction enzymes resulted in fragments characteristic of the restriction fragment length polymorphism patterns of H. pylori isolates from humans. In the domestic cat, H. pylori infection is associated with a lymphofollicular gastritis, consisting of lymphocytic and plasmacytic infiltration into the lamina propria, and the organism appears to provide chronic antigenic stimulation resulting in the formation of gastric lymphoid follicles.