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This study examined the effect of high, normal, and uncontrolled end-tidal Pco₂ (Pet_CO2) on the ventilatory, peak cerebral blood flow velocity (V̄_p), and mean arterial blood pressure (MAP) responses to acute hypoxia. Nine healthy subjects undertook, in random order, three hypoxic protocols (end-tidal Po₂ was held at eight steps between 300 and 45 Torr) in conditions of hypercapnia, isocapnia, or poikilocapnia (Pet_CO2 +7.5 Torr, +1.0 Torr, or uncontrolled, respectively). Transcranial Doppler ultrasound was used to measure V̄_p in the middle cerebral artery. The slopes of the linear regressions of ventilation, V̄_p, and MAP with arterial O₂ saturation were significantly greater in hypercapnia than in both isocapnia and poikilocapnia (P < 0.05). Strong, significant correlations were observed between ventilation, V̄_p, and MAP with each Pet_CO2 condition. These data suggest that 1) a high acute hypoxic ventilatory …