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 response (AHVR) decreases the acute hypoxic cerebral blood flow responses during poikilocapnia hypoxia, due to hypocapnic-induced cerebral vasoconstriction; and 2) in hypercapnic hypoxia, a high AHVR is associated with a high acute hypoxic cerebral blood flow response, demonstrating a linkage of individual sensitivities of ventilation and cerebral blood flow to the interaction of Pet_CO2 and hypoxia. In summary, the between-individual variability in AHVR is shown to be firmly linked to the variability in V̄_p and MAP responses to hypoxia. Individuals with a high AHVR are found also to have high V̄_p and MAP responses to hypoxia.