Gastric Helicobacter mustelae was present in 100% of 11 adult female ferrets (Mustela putorius furo). The high immunoglobulin G antibody levels to H. mustelae in all ferrets showed a significant immune response to the organism. Urease mapping of the ferret stomach indicated that the bacteria heavily colonized the proximal duodenum and antrum and, to a lesser extent, the corpus. The histological gastritis observed coincided with presence of H. mustelae. Superficial gastritis was noted in the oxyntic gastric mucosa, whereas in the distal antrum the chronic inflammatory response occupied the full thickness of the mucosa. In the proximal antrum and transitional mucosa, focal glandular atrophy and regeneration were observed. Seven control specific-pathogen-free ferrets were not colonized with the bacteria, did not have detectable levels of immunoglobulin G H. mustelae antibody, and did not have H. mustelae-associated gastritis. The ferret lacks the polymorphonuclear-cell response seen in active chronic gastritis typically described with Helicobacter pylori gastritis in humans. However, the lesion in ferrets does closely resemble the diffuse antral gastritis seen in a subset of adults with H. pylori gastritis as well as children infected with H. pylori. Like H. pylori, H. mustelae adheres tightly to gastric mucosa. The ferret infected with H. mustelae, in addition to specific-pathogen-free uninfected control ferrets, will make longitudinal studies possible, enabling dissection of multiple host and environmental variables that influence the effect of H. mustelae colonization on progression and severity of gastroduodenal disease.