The stability of the pulmonary blood pressure and flow response to alveolar hypoxia (hypoxic pulmonary vasoconstriction or HPV) was studied in six pentobarbital anesthetized, mechanically ventilated open-chested dogs. Aortic and left pulmonary artery blood flows; systemic and pulmonary arterial, central venous, left atrial, and airway pressures; hemoglobin; arterial and mixed venous blood gases were measured. The right lung was ventilated continuously with 100% oxygen, while the left lung was ventilated alternately with 100% O2 (prehypoxia control phase), an hypoxic gas mixture containing 4% O2, 3% CO2, balance N2 for 4 h, or 100% O2 (post-hypoxia control phase). Hypoxic ventilation of the left lung resulted in an immediate and sustained decrease in left lung blood flow (QL%) from 39.0+/-1.8%(mean+/-SE) to 9.9+/-3.6% at 15 min of hypoxic ventilation. QL% remained decreased and did not vary significantly during the 4 h of hypoxia. Venous admixture correspondingly was increased and PaO2 decreased by hypoxic ventilation and did not vary significantly during the 4 h of hypoxia. All variables returned to control levels upon reestablishing ventilation with 100% O2. While the maximal reduction in QL% with left lung hypoxic ventilation was identical to that observed during atelectasis previously in our laboratory, the time course of the response was different. The response to hypoxia was maximal by 15 min, however, QL% decreased more slowly during atelectasis, where the maximal reduction was observed by 60 min. The present study therefore demonstrated that hypoxic ventilation of the left lung yielded an immediate and sustained decrease in left lung blood flow for 4 h. The stability of the HPV response probably was accounted for by the lack of such confounding factors as respiratory alkalosis, severe systemic hypoxemia, and increased cardiac output.