Background & Aims: Oral immunization with recombinant Helicobacter pylori urease (rUre) coadministered with a mucosal adjuvant protects mice against challenge with Helicobacter foils, In this study, the duration of protection and gastritis after challenge were characterized at sequential time intervals up to 1 year, Methods: Outbred Swiss-Webster mice were orally immunized with rUre plus adjuvant and examined for the presence of H. foils infection and leukocyte infiltration into the gastric: mucosa, Results: When defined by gastric urease activity, 70%-95% of rUre-immunized mice were protected for between 2 and 57 weeks. Challenge with H. felis increased the inflammatory response Tn the gastric mucosa of rUre-immunized mice, which also had elevated CD4(+) and CD8(+) T cells. The CD8(+) cells represented a population of gastric intraepithelial cells, which expressed the mucosal alpha(E)-integrin, Epithelial changes consisting of parietal cell loss and hyperplasia of the epithelium occurred in approximately 20% of the mice. Antimicrobial triple therapy significantly decreased the degree of gastritis and epithelial alteration in the stomach, Conclusions: These results indicate that oral immunization of mice with rUre produces a long-lasting inhibition of H. felis infection but that residual bacteria may produce a persistent lymphocytic infiltration under these experimental conditions.