In 24 unanesthetized dogs, we monitored reactive hyperemia responses in the coronary vascular bed after different durations of coronary occlusion and during coronary artery reperfusion. After two hours of occlusion, no significant changes in functional capacity occurred, evidenced by unchanged peak reactive hyperemia, reactive hyperemia flow and repayment of flow debt responses. With occlusions of six hours or more, these responses were impaired upon reperfusion, and remained diminished for up to five days. In those animals reperfused after two and six hours of coronary occlusion, myocardial infarcts were significantly smaller than those seen in animals reperfused after 24 to 72 hours of occlusion (4%, 14%, 20% and 21%, respectively). Thus, the effectiveness of any reperfusion procedure depends on its early institution when the coronary vascular bed has minimal change in functional capacity and the size of the infarct can still be reduced.