A rat model of severe nerve ischemia was used to study the effects of ischemia and reperfusion on nerve conduction, blood flow, and the integrity of the blood-nerve barrier. Conduction failure was consistently found in the sciatic-tibial nerve during 1- and 3-hr ischemic periods. Recovery of the compound muscle action potential was prompt and complete upon reperfusion following 1 hr of ischemia. However, after 3 hr of ischemia, recovery in the proximal portion of the sciatic nerve was less than 10%, and conduction block occurred in the distal portion of the nerve. Nerve blood flow was restored to only 55% and 45% of resting values following 1 and 3 hr, respectively, of ischemia and did not recover even after 2 hr of reperfusion. The blood-nerve barrier was not statistically impaired to the passage of [14C]sucrose following 1 hr of ischemia but was significantly impaired after 3 hr of ischemia. The permeability-surface area product was consistently greater following 1 hr of reperfusion than during the immediate reperfusion period. These data indicate that severe ischemia of peripheral nerve results in reperfusion injury, conduction block, and blood-nerve barrier disruption. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fiber damage that began during ischemia.