Background and Purpose Transcranial Doppler (TCD) monitoring of mean blood flow velocity (mV) during head-upright tilt can allow testing of cerebral autoregulation. Nonetheless, head-upright tilt can induce changes in the ventilation-perfusion relationship and/or respiratory activity that might influence TCD data. Methods Forty-eight healthy volunteers underwent monitoring of mV and end-tidal CO2 in the horizontal position and during head-upright tilt. Results Both mV and end-tidal CO2 significantly decreased in orthostasis (P<.01). Linear regression analysis showed a significant linkage between end-tidal CO2 and mV changes (r=.83, P<.01). Conclusions Changes in ventilation-perfusion ratio and in the respiratory pattern induced by head-upright tilt can significantly influence TCD data by determining a PCO2, decrease.