During wakefulness, cerebral blood flow (CBF) is closely coupled to regional cerebral metabolism; however CBF is also strongly modulated by breathing, increasing in response to both hypercapnia and hypoxia. During stage III/IV non-rapid eye (NREM) sleep, cerebral metabolism and CBF decrease whilst the partial pressure of arterial CO2 increases due to a reduction in alveolar ventilation. The reduction in CBF during NREM sleep therefore occurs despite a relative state of hypercapnia. We have used transcranial Doppler ultrasound to determine middle cerebral artery velocity, as an index of CBF, and have determined that NREM sleep is associated with a reduction in the cerebrovascular response to hypercapnia. This reduction in reactivity would, at least in part, allow the observed reductions in CBF in this state. Similarly, we have observed that the CBF response to hypoxia is absent during stage III/IV NREM sleep. Nocturnal hypoxia and hypercapnia are major pathogenic factor associated with cardio-respiratory diseases. These marked changes in cerebrovascular control that occur during sleep suggest that the cerebral circulation may be particularly vulnerable to cardio-respiratory insults during this period.