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 (Qover dotS/Qover dotT) was measured by using blood gas analysis and by quantitation of the percentage of blood flow to the collapsed left lung (Qover dotLl/Qover dotT) using fluorescent microspheres. In control rabbits, Qover dotS/Qover dotT and Qover dotLl/Qover dotT decreased over time, whereas arterial PO2 increased. In hemodiluted rabbits, there was a trend toward increased Qover dotS/Qover dotT and Qover dotLl/Qover dotT. There were significant differences in the behavior of Qover dotS/Qover dotT, Qover dotLl/Qover dotT, 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, Qover dotS/Qover dotT and Qover dotLl/Qover dotT 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.