We tested the hypothesis that decreases in alveolar O2 pressure (PAO2) of a large lung compartment would, through decreases in arterial O2 pressure (PaO2) and mixed venous O2 pressure (PVO2), result in decreases in PAO2 of the remaining small lung compartment; thus large-compartment hypoxic pulmonary vasoconstriction (HPV) would be accompanied by concomitant small-compartment HPV. In eight pentobarbital-anesthetized dogs, whose left lower lobe (LLL) inspired oxygen concentration (FIO2) was constantly 0.21, selective stepwise reductions in the rest of the lung (RL) FIO2 from 1.0 to 0.15 caused the electromagnetically measured LLL blood flow (QLLL/Qt), pulmonary vascular resistance of RL (PVRRL), and PVRLLL to increase while RL PAO2, PaO2, PVO2, and LLL PAO2 progressively decreased. Stepwise reductions in RL FIO2 from 0.15 to 0.06 caused QLLL/Qt and PVRRL to decrease, PVRLLL To further increase, while RL PAO2, PaO2, PVO2, and LLL PAO2 progressively decreased further. Based on previously established PAO2 levels of maximum HPV gain and LLL dose-response curves, the RL FIO2-induced changes in QLLL/QT can be explained by different rates of change in RL and LLL PAO2 and PVR. Thus, our findings indicate that if decreases in RL FIO2 cause, in turn, large decreases in PaO2, PVO2 and "normoxic" lung PAO2, then PVO2 is an important determinant of the magnitude of the HPV response.