Threshold alveolar-arterial Pco2 (PtCOCO2) for the respiratory system in acute hypoxia of anesthetized dogs was examined by observing phrenic nerve discharges. It was found that 1) the lower the alveolar Po2, the lower the PtCOCO2. The relationship between the PaOO2 and the PtCOCO2 was curvilinear, PtCOCO2 showing an abrupt fall in the range of PaOO2 of 30–60 mm Hg. 2) The respiratory drive induced by hypoxia was completely extinguished by lowering alveolar Pco2. Thus it was proved that, during intense hypoxia, respiratory drive continues to be attributable to Pco2 or cH, even when they have been reduced far below normal. 3) Ventilatory response related to the hypoxic drive with other parameters constant was calculated from the nonhypoxic and hypoxic PtCOCO2 differences and from the ventilatory coefficients. It was then inferred that a positive interaction between Po2 and Pco2 or cH stimulus for ventilation exists when PaOO2 falls below about 70 mm Hg. Pco2 levels in acute hypoxia; dogs