AbstractINTRODUCTION As an introduction t o the first book on the subject of omeprazole it might be of interest to mention a few steps in the development of this compound. The anti-ulcer research project was started as early as 1966-67. The initial aim was to find a drug that caused inhibition of gastric acid secretion by blocking release of gastrin from the antrum. The chemical lead compound was the local anaesthetic agent lidocaine. The aim of the project was to develop compounds that retained the local anaesthetic properties in an acidic environment. In 1972 compunds without local anaesthetic properties but with a pronounced antisecretory effect in the rat were found. One of these substances was brought to human pharmacological studies. It was, however, devoid of antisecretory activity in man. The research project was resumed from a different angle. The aim was now to find an antisecretory drug without anticholinergic or histamine H,-blocking properties. The screening model was changed to the pentagastrin stimulated gastric fistula dog and the chemical lead was a pyridinethioacetamide, CMN 13 1 . This substance had a high acute toxicity and the first aim was to identify the essential structural elements behind the antisecretory effect.