We evaluated the regional myocardial blood flow in collateral dependent infarct-related areas to examine the functional role of coronary collaterals. Regional myocardial blood flow was measured by positron emission tomography with 13N-ammonia at rest and during low-grade exercise (bicycle ergometer fixed at 25 W for 6.5 min). The study was performed in 24 subjects, consisting of 19 patients with prior myocardial infarction, and five normal individuals. Regional myocardial blood flow was calculated using the radioactivity in myocardial tissue measured by positron emission tomography and the radioactivity in arterial blood. Concerning the infarct related area, the exercise caused myocardial blood flow to decrease by 18.4% (P < 0.01) in the collateral-dependent areas (n = 8) of angiographically positive collaterals, and to increase by 14.4% (P = not significant) in the areas (n = 10) of negative collaterals. Four patients in whom the myocardial blood flow in all walls, including the normal areas, decreased with exercise were excluded from this evaluation. Myocardial blood flow in collateral-dependent infarct-related areas appeared to decrease transiently by low-grade exercise. Our results suggest that collaterals increase the incidence of exercise-induced ischemia, but may protect the infarct related but viable myocardium from necrosis.