The incomplete restoration of blood flow during reperfusion may amplify injury by prolonging ischemia; this "no-reflow" has been studied extensively in systemic organs. Our goal was to examine lung blood flow and microvascular function, specifically to determine whether blood flow is altered during lung reperfusion injury in vivo. In a unilateral lung model of ischemia-reperfusion in awake sheep, we measured pulmonary vascular resistance in each lung by radiolabeled microspheres. Measurements were made before 14 h of ischemia and again 4 h after reperfusion. Vascular resistance in the reperfused lung increased 3-fold (9.64 +/- 0.85 to 27.04 +/- 4.73 cm H2O/L/min) during reperfusion. The increase in vascular resistance in the reperfused lung fully accounted for the small increase in overall pulmonary vascular resistance (4.04 +/- 0.26 to 5.52 +/- 0.70 cm H2O/L/min). Microvascular permeability in the reperfused lung increased 52% more than in the contralateral lung, measured by an improved indicator dilution method with additional markers sensitive to surface area (butanediol). We conclude that changes in vascular resistance and microvascular function occur during lung reperfusion injury in vivo. The demonstration that postischemic hypoperfusion occurs during lung reperfusion in vivo suggests possible new avenues of approach to related clinical disorders.