We compared the efficacy of intra-arterial infusion of urokinase, a fibrinolytic agent, with that of intra-arterial infusion of nitrendipine, a peripheral calcium-channel blocking agent, in preventing the no-reflow phenomenon in rats after prolonged ischemia at room temperature. Urokinase increased the survival of the limbs after both four and five hours of ischemia at room temperature to 100 per cent compared with 50 and 20 per cent, respectively, in untreated controls. Nitrendipine significantly increased the blood flow but failed to significantly increase the survival of the limb. Scanning electron microscopy was used to assist in the evaluation of the endothelium of the vessels. The etiological mechanism of the no-reflow phenomenon appears to be that ischemia damages the endothelial cells, causing impairment of the fibrinolytic system, retraction of the endothelial membrane, exposure of the subintimal collagen, and fibrin-platelet deposition. Thrombosis of the vessels ensues, resulting in the no-reflow phenomenon. Clinical Relevance: Experimentally, intra-arterial infusion of urokinase increased the survival of the limb in replanted extremities that were subjected to ischemia. This effectively lengthened the safe limit of ischemia at room temperature before microsurgical replantation or elective free-tissue transfer. Clinical trials of the use of intra-arterial fibrinolytic agents for the treatment of revascularized tissue are indicated.