Changes in permeability following ischemia-reperfusion injury were assessed in the intact rabbit hindlimb by measuring the transvascular clearance of I-125-labeled rabbit serum albumin. Ischemia was induced for periods of 1 or 2 hours by use of a pneumatic tourniquet inflated to 300 mmHg. Following ischemia, the limb was reperfused for 1, 2, or 3 hours. The albumin clearance in the gastrocnemius muscle of control rabbits was 3.1 +/- 0.7 (mean +/- SEM) mul/hr/g dry weight. Following 1 hour of ischemia and reperfusion, muscle albumin clearance rose to 71.4 +/- 26 mul/hr/g dry weight which was not significantly different from those animals that underwent 2 hours of ischemia. Muscle albumin clearance continued to be elevated following 2 hours of reperfusion; however, it returned toward control levels after 3 hours of reperfusion. These data suggest there is a transient increase in albumin permeability following ischemia-reperfusion injury in skeletal muscle.