A multifactorial basis has been shown to exist in the development of gastric damage induced by aspirin and related N.S.A.I. drugs. Aspirin-induced gastric damage is characterized by a variety of physical and biochemical changes induced in the gastric mucosa which occur at different stages after administration of the drug. Aspirin only causes gastric ulceration and massive haemorrhage in the stomach when the stomach has been sensitized by the prior exposure to moderate stress conditions (which may resemble anxiety or psychologic stress). A model of ulcer development in which aspirin or other N.S.A.I. drugs are given to rats or pigs exposed to brief periods of stress has been described. Using this more sensitive assay procedures can be explored for reducing the gastric damaging effects of N.S.A.I. drugs. One such procedure involves chemical modification of the carboxylic acid moiety of aspirin.