Since the ability of mature intercoronary collateral channels to increase myocardial blood flow in response to drug induced coronary vasodilation has been questioned, the present study was undertaken to evaluate the response of coronary collateral circulation to the stress of exercise. Studies were performed at rest and during two levels of treadmill exercise in six dogs a minimum of 6 mo after placement of an Ameroid constrictor on the left circumflex coronary artery. Regional myocardial blood flow was estimated in normally perfused anterior and predominantly collateral dependent posterior left ventricular wall with left atrial injections of radionuclide labeled microspheres 7-10 μm in diameter. At rest, heart rate was 87±7 beasts/min and mean myocardial blood flow was comparable in control and collateral dependent regions (0.96±0.13 and 0.97±0.14 ml/min . g, respectively). During exercise, heart rates increased to 180±13 and 228±14 beats/min and myocardial blood flow (MBF) in the anterior control region increased linearly with heart rate (HR), (MBF=0.133 HR-0.202, r=0.88). MBF to the posterior collateral dependent region was similarly augmented during exercise (MBF=0.140 HR-0.252, r=0.89), so that the linear correlation between HR and MBF was similar for the control and collateral dependent regions. In addition, the transmural distribution of MBF was uniform at rest and during exercise in both the anterior control and posterior collateral dependent regions. Thus, not only could the mature intercoronary collateral vasculature supply adequate flow at rest, but when subjected to the natural stress of exercise, the increase in flow to the predominantly collateral dependent area was similar to that in the normally perfused area.