To elucidate the effects of anemia on intrapulmonary shunt, we studied a model of left lung atelectasis in anesthetized rabbits. In 10 rabbits, isovolemic anemia was produced by sequential hemodilution. Seven control rabbits were followed over time, without hemodilution. Intrapulmonary shunt (Qs/QT) was measured by using blood gas analysis and by quantitation of the percentage of blood flow to the collapsed left lung (QLl/QT) using fluorescent microspheres. In control rabbits, Qs/QT and QLl/QT decreased over time, whereas arterial PO2 increased. In hemodiluted rabbits, there was a trend toward increased Qs/QT and QLl/QT. There were significant differences in the behavior of Qs/QT, QLl/QT, and arterial PO2 between control and hemodiluted rabbits. Hemodynamic parameters, including cardiac output and pulmonary artery pressure, were not different between groups. In a third group of rabbits with pharmacologically induced acidosis but no hemodilution, Qs/QT and QLl/QT decreased over time, and arterial PO2 increased. We conclude that acute isovolemic anemia has a deleterious effect on pulmonary gas exchange, possibly through attenuation of hypoxic pulmonary vasoconstriction.