A continuous, adherent mucus gel layer with mucosal bicarbonate secretion is the initial protective barrier in the stomach and duodenum against erosion by the gastric juice. H. pylori resides within the adherent mucus gel layer close to the epithelial surface. The barrier function of the mucus layer in vivo depends on (i) its thickness, and (ii) its gel structure, a property which is linearly dependent on the polymeric mucin content. We have shown in vivo that H. pylori colonisation alone did not decrease the thickness of the adherent gastric mucus barrier, although there was a mean 20% decrease in mucus thickness in those H. pylori positive subjects with underlying gastric atrophy. There was, however, a significant mean 18% reduction in the gel-forming polymeric mucin content of mucus from H. pylori subjects, independent of underlying atrophy. Studies in vitro suggest this loss of gel structure might arise from a H. pylori mediated, high local pH generated by urease activity rather than by proteolysis. This study shows that H. pylori infection alone does not compromise the overall integrity of the mucus barrier in vivo. However, in the immediate environment of the organism there appears to be a localised loss of mucus gel structure. The mucus barrier is compromised if H. pylori associated gastric atrophy or peptic ulceration follows.