A layer of water-insoluble mucus gel has been shown to form a continuous cover over the gastroduodenal mucosal surfaces, of median thickness of 180 micron in stomach in humans. This adherent mucus is the first line in mucosal defence against the natural aggressors, acid and pepsin, in the lumen. Mucus gel provides a stable unstirred layer that supports surface neutralisation of acid by mucosal bicarbonate. Mucus gel is a diffusion barrier to pepsin in the lumen, preventing proteolysis of the underlying epithelial cells. There is, however, a dynamic balance between digestion by pepsin of the mucus layer at its luminal aspect and secretion of new mucus by the epithelium. There is evidence that, in peptic ulcer disease, the rate of peptic degradation of the mucus barrier is increased. Exogenous damaging agents such as ethanol and aspirin permeate the gel matrix of the mucus barrier, rapidly damaging the underlying epithelium. The subsequent reepithelialisation process is protected by a gelatinous coat over ten times thicker than the original adherent mucus layer. This gelatinous coat is primarily a fibrin-based gel with necrotic cells and mucus.