In the upright position cerebral blood flow is reduced maybe because arterial carbon dioxide partial pressure (P_a,CO2) decreases. We evaluated the time-dependent influence of a reduction in P_a,CO2 as indicated by the end-tidal P_CO2 tension (P_ET,CO2) on cerebral perfusion during head-up tilt. Mean arterial pressure, cardiac output, middle cerebral artery mean flow velocity (MCA Vmean), and dynamic cerebral autoregulation at supine rest and 70° head-up tilt were determined during free breathing and with P_ET,CO2 clamped to the supine level. The postural changes in central hemodynamic variables were equivalent and the cerebrovascular autoregulatory capacity was not significantly affected by tilt or by clamping P_ET,_CO2. In the first minute of tilt, the decline in MCA V_mean (10 ± 4 vs. 3 ± 4 cm s^-1; mean ± S.E.M; P < 0.05) and P_ET,_CO2 (6.8 ± 4.3 vs. 1.7 ± 1.6 mmHg; P < 0.05) was larger during spontaneous breathing than during isocapnic tilt. However, after two minutes in head-up position, the reduction in MCA V_mean was similar (7 ± 5 vs. 6 ± 3 cm s^-1), although the spontaneous decline in P_ET,CO2 was maintained (P < 0.05 vs. isocapnic tilt). These results suggest that the potential contribution of P_a,CO2 to the postural reduction in MCA V_mean is transient, leaving the mechanisms for the sustained restrain in MCA V_mean to be identified.