Carriage of the bacteriumH. pyloriin the human stomach is associated with evidence of increased epithelial cell apoptosis. This may be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. The ability ofH. pylorito directly induce epithelial apoptosis was examinedin vitroby fluorescence and electron microscopy, flow cytometry, and DNA fragmentation ELISA. The induction of apoptosis byH. pyloriwas time and concentration-dependent and inhibited by preventing direct bacterial-epithelial cell contact. Apoptosis was accompanied by increased expression of Bak, with little change in expression of other Bcl-2 family proteins. The expression of Bak was also increased in gastric biopsies from patients colonized byH. pylori.Thus,H. pyloriinduces gastric epithelial cell apoptosis, by a Bak-dependent pathway.