In the stomach several mucosal defence mechanisms protect the stomach against hydrochloric acid and noxious agents. The pre-epithelial protection is made up by the mucus-bicarbonate barrier. Mucus and bicarbonate, secreted by mucus cells, create a pH gradient maintaining the epithelial cell surface at near neutral pH. In humans, secretion of bicarbonate is an active process and is activated by vagal stimulation and fundic distension. Several mechanisms at the epithelial cell level contribute to an intact mucosal barrier. Surfactants in apical cell membranes prevent water-soluble agents in the gastric lumen from reaching and damaging the epithelium. Nonprotein sulphydryls in the epithelium are capable of binding reactive free radicals. Rapid cell turn-over and the process of restitution contribute to an intact epithelial lining. In subepithelial protection, mucosal blood flow is essential in supplying the epithelium with nutrients and oxygen and for disposal of hydrogen ions and noxious agents permeating the mucosa. Prostaglandins may maintain blood flow and prevent vascular endothelial injury caused by ethanol. Several agents have been established as protective for the gastric mucosa. Prostaglandins possess direct cytoprotective actions, whilst sucralfate, aluminium containing antacids, carbenoxolone and bismuth are mild irritants that induce liberation of endogenous prostaglandins of the mucosa.