The purpose of this study was to quantify the possible reduction in ventilation that could be attributed to changes in cerebral blood flow (CBF) with hypoxia to determine whether it could be of sufficient magnitude to underlie hypoxic ventilatory decline (HVD). Six subjects underwent 20 min of isocapnic hypoxia (end-tidal PO2, 50 mmHg). An index of CBF was obtained using transcranial Doppler ultrasound of the middle cerebral artery. The CBF sensitivities to hypoxia and hypercapnia were obtained from the percentage changes in CBF between the last 3 min of the hypoxic or hypercapnic exposure and the 3 min period prior to the exposure. The magnitude of HVD during hypoxia was estimated by fitting a simple model of the ventilatory response to the hypoxic stimulus. The predicted fall in expiratory ventilation ([Vdot]E) due to a reduction in brain PCO2 generated by the increase in CBF with hypoxia in all subjects was less than the measured magnitude of HVD (33 %). Thus, the results from this study suggest that, in awake humans, changes in CBF during acute isocapnic hypoxia are quantitatively insufficient to underlie HVD in humans.