The gastric spirillum Helicobacter felis, originally isolated from the cat stomach, colonizes the stomachs of germfree rats. Studies were designed to examine the pathological and serological responses of germfree rats inoculated orally with H. felis. At 2 weeks postinoculation, the gastric mucosa of germfree rats had lymphocytes and eosinophils scattered in small foci throughout the subglandular region of the antrum. Small numbers of lymphocytes were present in the subglandular portion of the antral mucosa that focally extended through the lamina propria towards the luminal surface. Eight weeks postinoculation, the inflammation was confined to the antrum. It was characterized by increased numbers of lymphocytes and eosinophils in the subglandular areas, with focal aggregates of lymphocytes in the submucosa. Some lymphoid aggregates extended from the submucosa through the muscularis mucosa and lamina propria to the luminal surface. H. felis was demonstrated with the Warthin-Starry stain, bacterial culture, and urease assay, particularly in the antrum. H. felis also produced a significant immunoglobulin G antibody titer at 2, 4, and 8 weeks postinoculation as well as a transitory immunoglobulin M response at 2 to 4 weeks postinoculation. Contact control rats were not infected, inferring that fecal-oral spread of H. felis did not occur.