In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.