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1. The reactivity of coronary arteries to noradrenaline (NA), acetylcholine (ACh) and isoprenaline (Iso) during acute myocardial ischaemia was studied in anaesthetized, open-chest dogs. 2. The left anterior descending coronary artery (LAD) was cannulated and perfused via an extracorporal circuit at constant flow. Ischaemia was produced by decreasing the perfusion blood flow of the LAD to 50% (moderate ischaemia) and 27% (severe ischemia) of normal. A dose of each agent which had no significant myocardial effects was chosen. Heart rate was held constant by ventricular pacing during ACh administration. 3. Under normal conditions, the infusion of NA, ACh and Iso into the LAD produced significant decreases in coronary vascular resistance (P less than 0.01). However, under either moderate or severe ischaemic conditions intracoronary NA resulted in a marked increase in coronary vascular resistance (P less than 0.01), which was completely blocked by phentolamine, an alpha-adrenoceptor blocker; intracoronary ACh and Iso did not have a significant effect on coronary vascular resistance (P greater than 0.05). 4. These results indicate that coronary arterial responsiveness to some intrinsic vasoactive substances, such as NA and ACh, is altered during acute myocardial ischaemia. This may be important in the pathophysiology of myocardial ischaemia.