Physiological regulatory mechanisms of gastric acid secretion are the basis for all those studies which attempt to analyze the pathophysiological role of acid secretion. The major stimulus of parietal cell function is food intake which acts via activation of cephalic-vagal and gastric mechanisms. Cephalic phase of acid secretion is augmented predominantly by acetylcholine and gastrin while histamine is of major importance during the gastric phase. A contribution of neuropeptides located in the ex- and intrinsic nervous system such as enkephalin, beta-endorphin, gastrin-releasing peptide and neuromedin C ist most likely, however, their exact physiological role remains to be determined especially in man. Following maximal acid secretion parietal cell function is turned down which is paralleled by the decrease of intragastric pH. The mechanisms responsible for this effect originate in the stomach and small intestine. In contrast to the stimulatory factors the physiologically relevant inhibitors of acid secretion are less well known. Hormones such as somatostatin, glucagon-like peptide-1 (7-36)-NH2 and peptide YY are presumably of importance. The role of secretin, GIP, CCK and neurotensin is somewhat more controversial and remains to be examined in greater detail in humans. Especially the synergistic action of gastrointestinal hormones is virtually unknown. The increasing knowledge of the complex regulatory mechanisms in the stomach should result in new perspectives for the pathogenesis of peptic ulcer disease.