Tumor necrosis factor- (TNF-) and interferon- (IFN-) are important for the pathogenesis of Helicobacter pylori-associated gastritis and peptic ulcer disease. Gastric biopsies from H. pylori-positive and -negative patients were used to examine the in situ correlation of TNF- and IFN- with epithelial cell apoptosis, bacterial load, and histological parameters of gastritis. From the same patients, we isolated H. pylori-specific T cell lines and clones and examined their ex vivo release of proinflammatory cytokines. We found a highly significant correlation of TNF- and IFN- production with activity and grade of gastritis (P < 0.01), H. pylori density (P = 0.01), epithelial cell apoptosis (P < 0.001), and Fas/Fas-ligand expression (P < 0.001). T cell lines and clones were all TCR-⁺ and showed T helper 1 functional phenotype. With the use of serial histological sections, this study showed for the first time the in situ correlation of TNF- and IFN- with epithelial cell apoptosis, bacterial load, and histological severity of disease and emphasizes the role of these cytokines in the pathophysiology of H. pylori-associated disease.