Helicobacter pylori infection of human gastric epithelium has been associated with gastritis, ulcers and gastric cancers. In an H. felis, germ-free mouse model of infection, oral immunization with bacterial antigens plus cholera toxin resulted in elevated serum, gastric and intestinal anti-H. felis antibody titres and protection from acute infection. Mice given monoclonal IgA anti-H. felis antibody at the time of initial challenge were also protected from infection. These results demonstrate that oral vaccination may be a feasible approach for the prevention of H. pylori infection of humans.