We hypothesized that establishing conditions of hypoxia and fluid filling of the airways in lungs of newborns would reproduce the high levels of pulmonary vascular resistance (PVR) observed in the fetal state. We assessed the hemodynamics of the left pulmonary circulation of 1- to 3-day-old lambs during a variety of airway states while attempting to reestablish fetal conditions. Eleven animals were studied during both normoxemia and hypoxemia in a baseline airway state with a positive end-expiratory pressure (PEEP) of 4 cm H2O, and in experimental airway states, of atelectasis, and fluid filling to 15 and 30 mL/kg and with PEEP of 12 cm H2O. PVR increased while pulmonary blood flow decreased with all airway state changes as compared to baseline, suggesting a passive mechanism for these changes. With the addition of hypoxemia there was a further increase in PVR in all states accompanied by an increase in pulmonary blood flow, indicating that active vasoconstriction was responsible for the increase in PVR. The combined effects of hypoxemia and fluid filling, designed to approximate the fetal state, increased PVR to only 20-30% of fetal values. Thus, additional factors appear to be important in maintaining the high PVR of the fetal state. We speculate that ventilation of the lungs at birth irreversibly alters these factors.