Background and Aims: Orogastric immunization of mice with Helicobacter antigens, together with a mucosal adjuvant (cholera toxin), has been shown to confer immunity in the Helicobacter fells infection model. The aim of the study was to investigate the humoral immune responses associated with immunity and to compare these with responses in H. felis-infected mice. Methods: Enzyme-linked immunoassays were used to characterize the antibody- secreting cells and antibodies present at mucosal and systemic sites in mice. Animals were immunized orally with either whole-cell H. felis sonicates or Helicobacter pylori urease or heat-shock proteins. Results: Infection of mice with H. felis preferentially induced the recruitment of plasma cells committed to immunoglobulin (Ig) A synthesis in salivary gland and gastric tissues. Antigen-specific IgA was the major antibody class detected in mucosal secretions recovered from these tissues. In contrast, immunization of mice against H. felis infection induced the proliferation of large numbers of IgG-secreting cells, as well as the synthesis of local IgG antibodies, in the gastric mucosa of the animals. Protection against H. fells infection occurred in the absence of gastric IgA responses in sonicate-immunized mice. Conclusions: It is proposed that locally synthesized specific IgG antibodies contribute to immunity against gastric Helicobacter infection.