Significant coronary artery disease may exist in a patient despite a normal resting electrocardiogram and a negative history. A standardized 2-step exercise is recommended as a simple diagnostic test of ischemic heart disease. This master test was applied to 596 subjects whose resting electrocardiograms were normal. In 277 the electrocardiograms after exercise were classified as normal by criteria developed by the authors, and from 1952 to 1961, 96.8% of this "negative" group remained free from clinical evidence of heart disease. In the other 319, electrocardiograms after exercise showed various types of depressions of the RS-T segment below the isolectric line. The significance of these changes and other criteria was evaluated. It is concluded that 95% of patients with significant coronary disease show abnormalities of the electrocardiogram after exercise which satisfy the criteria set forth by the authors.