Changes in the partial pressure of arterial CO2 (PaCO 2) regulates cerebrovascular tone and dynamic cerebral autoregulation (CA). Elevations in PaCO2 also increases autonomic neural activity and may alter the arterial baroreflex. We hypothesized that hypercapnia would impair, and hypocapnia would improve, dynamic CA and that these changes would occur independently of any change in baroreflex sensitivity (BRS). In 10 healthy male subjects, incremental hypercapnia was achieved through 4-min administrations of 4% and 8% CO2. Incremental hypocapnia involved two 4-min steps of hyperventilation to change end-tidal PCO2, in an equal and opposite direction, to that incurred during hypercapnia. End-tidal, arterial and internal jugular vein PCO2 were sampled simultaneously at baseline and during each CO2 step. Dynamic CA and BRS was assessed at baseline and during each step change in PaCO2 using spectral and transfer-function analysis of beat-by-beat changes in mean arterial blood pressure (MAP), heart rate and flow velocity in the middle cerebral arterial (MCAv). Critical closing pressure (CCP), an estimate of cerebrovascular tone, was estimated from extrapolation of the MAP-MCAv waveforms. Hypercapnia caused a progressive increase in PaCO2 and MCAv whereas hypocapnia caused the opposite effect. Despite marked changes in CPP, there were no evident change in transfer-function gain, coherence, MAP variability or BRS; however, both MCAv variability and phase in the very-low frequency range was reduced during the most severe level of hyper- and hypocapnia (P <0.05), and were related to elevations in ventilation (R2=0.42-0.52, respectively; P<0.001). It seems that hyperventilation, rather than PaCO2, has an important influence on dynamic CA.