Symptoms resulting from diseases of the heart and those due to disorders of the gastrointestinal system are frequently so similar that it is difficult to determine which of the two systems is at fault. Both cardiac and upper gastrointestinal lesions may cause substernal or epigastric localization or both. The presence of a pre-existing cardiac or gastric disorder may further confuse the clinical picture. The most important conditions that closely simulate one another are defined and the pertinent differential diagnostic criteria outlined. Emphasis has also been directed to the possibility and importance of acute coronary disease occurring together with an acute ulcer of the stomach or duodenum caused by stress; this combination is frequently fatal unless recognized early and treated accordingly.