Bicarbonate secretion by the surface epithelium in the stomach and duodenum maintains a near neutral pH in the mucus gel adherent to the surface in spite of acidities as high as pH 2.0-3.0 in the gastric and pH 1.5-2.0 in the duodenal lumen. This strongly suggests that the alkaline secretion together with the mucus gel provides a first line of protection in the stomach and this may be the main mechanism of defense in the duodenum. The secretion is increased by physiological stimuli such as sham-feeding or the presence of acid in the lumen. Mucosal endogenous production of prostaglandins as well as humoral and neural mechanisms are involved in the control of the secretion.