Hypoxia is known to impair cerebral autoregulation (CA). Previous studies indicate that CA is profoundly affected by cerebrovascular tone, which is largely determined by the partial pressure of arterial O(2) and CO(2). However, hypoxic-induced hyperventilation via respiratory chemoreflex activation causes hypocapnia, which may influence CA independent of partial pressure of arterial O(2). To identify the effect of O(2) on dynamic cerebral blood flow regulation, we examined the influence of normoxia, isocapnia hyperoxia, hypoxia, and hypoxia with consequent hypocapnia on dynamic CA. We measured heart rate, blood pressure, ventilatory parameters, and middle cerebral artery blood velocity (transcranial Doppler). Dynamic CA was assessed (n = 9) during each of four randomly assigned respiratory interventions: 1) normoxia (21% O(2)); 2) isocapnic hyperoxia (40% O(2)); 3) isocapnic hypoxia (14% O(2)); and 4) hypocapnic hypoxia (14% O(2)). During each condition, the rate of cerebral regulation (RoR), an established index of dynamic CA, was estimated during bilateral thigh cuff-induced transient hypotension. The RoR was unaltered during isocapnic hyperoxia. Isocapnic hypoxia attenuated the RoR (0.202 +/- 0.003/s; 27%; P = 0.043), indicating impairment in dynamic CA. In contrast, hypocapnic hypoxia increased RoR (0.444 +/- 0.069/s) from normoxia (0.311 +/- 0.054/s; +55%; P = 0.041). These findings indicated that hypoxia disrupts dynamic CA, but hypocapnia augments the dynamic CA response. Because hypocapnia is a consequence of hypoxic-induced chemoreflex activation, it may provide a teleological means to effectively maintain dynamic CA in the face of prevailing arterial hypoxemia.