To study the effect of long-term coronary reperfusion on regression of newly developed collateral vessels, the authors reoccluded the coronary artery for ten minutes following one to fifteen weeks of reperfusion. They repeated one- or two-minute occlusions of the left circumflex coronary artery (LCCA) in 8 conscious dogs. After 401 +/- 202 (SD) minutes of total LCCA occlusion time (35 +/- 19 days), The LCCA occlusion produced no sustained reduction in regional myocardial shortening and negligible reactive hyperemia. Upon reocclusion following a long-term reperfusion, the subendocardial segment shortening in the region at risk deteriorated markedly. At two minutes of occlusion, percent systolic shortening showed minimal values and thereafter gradually returned to the preocclusion resting levels within six to eight minutes of occlusion. In the presence of a resting heart rate similar to that at the time of functional recovery during the LCCA occlusion, long-term reperfusion did not modify the time course of regional functional response to the prolonged coronary occlusion. It is concluded that the newly developed collateral vessels still serve as significant blood-conveying conduits following a considerable period of reperfusion, and it requires approximately six to eight minutes to restore regional myocardial function in the collateral dependent zone following coronary reocclusion.