Colonization by Helicobacter pylori of the acid-secreting tubules of gastric glands and the canaliculi of parietal cells has only rarely been reported. The presence of these organisms in such "deep" locations has only been reported in association with the more typical superficial colonization of the mucous gel layer overlying gastric epithelial cells. We report two cases of deep H. pylori infection without the presence of superficial organisms. Both patients had been using proton pump inhibitors for many years. We review the literature regarding the distribution of H. pylori within the stomach and the effect of proton pump inhibitor use on H. pylori distribution.