How the gastric mucosa is able to withstand intraluminal acid, which can attain concentrations approaching 155 mM H+ under conditions of maximal stimulation, remains an unanswered question. The concept of the gastric mucosa as a limiting barrier to ion diffusion developed from an appreciation that the concentration of electrolytes in the stomach varies with the rate of secretion. Thus gastric juice has a high Na+ and a low H+ concentration at low secretory rates, while at high secretory rates the reverse is found. 1 In addition it is well known that a reduction in H+ and gain in Na+ occursafter instillation of exogenous acid into the ligated stomach or gastric pouch. 23 Teorell4 considered the gastric mucosa as a diffusion barrier and described events at the mucosal surface in terms of an exchange diffusion between H+ in the lumen and Na+ in the mucosa. In contrast, Hollander5 proposed a two component barrier consisting of the mucus layer lining the gastric mucosa together with the subjacent layer of epithelial cells and suggested that the reduction in H+ concentration resulted from dilution and neutralisation by a Na+ containing non-acid secretion or leakage of interstitial fluid. The gastric mucosal barrier was sytematically studied by Davenport, 6 who considered it to beformed by the apical membrane of the surface epithelial cells together with the tight junctions linking adjacent cells. Competent tight junctions prevent diffusion of the gastric contents into the mucosa with loss of H+ from the lumen and entry of Na+ limited by this ion barrier. Numerous compounds which damage the stomach, including salicy-lates, alcohol, and bile salts, increase the permeability of the barrier inducing diffusion of acid into the mucosa with subsequent development of haemorrhage and mucosal erosion. 8 7 Whether or not back-diffusion of acid is a normal physiological process is uncertain and, indeed, a recent review of the question concluded that there is no direct evidence that the disappearance of H+ from the lumen of the stomach is caused by back-diffusion. 9 Whereas Davenport ascribed to mucus the chief function of lubrication, Heatley10 suggested that mucus played a major role in protecting the gastric epithelium by providing an unstirred layer on thesurface of the mucosa. He proposed that H+ diffusing in from the gastric lumen is neu-tralised by HCO3 secreted from the mucosa. Thus the mucus gel could provide an unstirred layer which maintains HCO3 at the mucosal surface and prevents it from mixing with bulk HCI in the lumen of the stomach. Until now there has been a lack of appropriate data to enable assessment of these hypotheses on the nature of mucosalprotection. However, recent work on two aspects of themucosal barrier-namely, the structure of the mucus gel11 1213 and the demonstration of an activeHCO3 secretion by surface epithelial cells14 15 16-has provided important new insights at themolecular 249