To identify mechanisms of immunity against Helicobacter pylori, we performed microarray analysis on gastric tissue from infected mice and mice vaccinated prior to challenge. RNA from gastric tissue was used to screen over 10,000 genes. MHC antigens and GTP binding proteins were upregulated in both groups. Infected mice were characterized by expression of innate host defense markers while immune mice expressed many IFN-gamma response genes and T cell markers. Results were confirmed for several genes by RT-PCR. CD4+ spleen cells from immune mice produced significantly more IFN-gamma than from infected mice. These results support a role for T cell regulated inflammation in H. pylori immunity.