The mucus barrier is a layer of water-insoluble gel adherent to the gastroduodenal epithelium. In man most previous studies have focused on luminal mucus or histological assessment of presecreted, intracellular mucus--neither of which can be directly correlated with the protective capacity of the adherent mucus barrier. We here describe direct observation of adherent mucus thickness in man, and changes in peptic ulceration. Adherent mucus gel on human antral mucosa is a continuous homogeneous layer of variable thickness, in the range 50-450 microns (median 180 microns), comprising 67% polymeric mucin. In gastric ulcer patients, adherent antral mucus is significantly increased in thickness (median 240 microns), but is very heterogeneous and structurally a substantially weaker gel, comprising only 35% polymeric mucin. Adherent antral mucus from duodenal ulcer patients is homogeneous, significantly thinner (median 110 microns), and structurally a weaker gel, comprising 50% polymeric mucin. The adherent mucus layer from patients with gastric carcinoma resembled that from subjects with gastric ulcer in that it was very heterogeneous, of significantly increased thickness (median 240 microns) and structurally a very weak gel (23% polymeric mucin). These results are discussed in the context of gastroduodenal mucosal protection against acid and pepsin in the gastric juice.