The membrane-bound ATP-dependent energy systems (ATP-membrane ATPase-ADP and ATP-adenylate cyclase-cAMP) play an essential role in the physiological regulation of the gastrointestinal mucosa and its damage in rat and man. A good, physiologically, hormonally and pharmacologically well controlled and regulated feedback system exists between the two energy systems. The significant increase of ATP transformation into ADP or cAMP represents a causative metabolic background of the development of gastric, duodenal and jejunal ulcer (damage) in man and rat. The ulcer preventive effects of vitamin A, beta-carotene, atropine, cimetidine, prostacyclin I2, and surgical vagotomy were studied in connection with their effects on the membrane-bound ATP-dependent energy systems of the gastric, duodenal and jejunal mucosa in man and rat. Atropine and cimetidine were applied in cytoprotective and antisecretory doses, and the tissue levels of ATP, ADP, AMP, cAMP and lactate were measured. The results indicated that the disturbed equilibrium between the two energy supply systems can be modified (normalized) by drugs and surgical vagotomy; the drug effect depends on the actual biochemism of the gastroduodenal mucosa; the values of affinities (pD2) and intrinsic activities (alpha) of the different drugs differ in relation to membrane-bound ATP-splitting enzymes; the changes in the membrane-bound ATP-dependent energy systems of the damaged rat gastric mucosa, produced by vitamin A and beta-carotene, depend on their cytoprotective doses which are connected with their cytoprotective effects; the biochemical changes induced by drugs (given in cytoprotective and anti-secretory doses) differ only quantitatively but not qualitatively; the drug effects on the membrane-located ATP-splitting enzymes (membrane ATPase and adenylate cyclase) in human gastric, duodenal and jejunal mucosa are similar to those in rats, but their affinities (pD2) and also their intrinsic activities (alpha) differ to the enzyme systems.