This study examines the effects of acute hypocapnia, instituted prior to reperfusion of the graft liver, on the middle cerebral artery (MCA) Doppler blood flow velocity response to reperfusion during orthotopic liver transplantation in humans. Seventeen patients with chronic liver disease underwent continuous, noninvasive Doppler imaging of the MCA. Hyperventilation to an end-tidal Pco(2) of 25 +/- 1 mm Hg was associated with a decrease in mean MCA flow velocity (FVm) from 51.6 +/- 5.7 to 37.0 +/- 3.3 cm/s (P < 0.05). After reperfusion, the Paco(2) increased from 32 +/- 1 to 40 +/- 1 mm Hg (P < 0.05), mean arterial pressure (MAP) decreased from 76 +/- 3 to 60 +/- 2 mm Hg, and the FVm increased from 37.0 +/- 3.3 to 54.0 +/- 4.7 cm/s (P < 0.05). FVm increased postreperfusion despite prior hyperventilation, decreased MAP, and abrupt increases in central venous and pulmonary artery pressures, but FVm did not exceed the prereperfusion level. In 10 of the 17 patients, the baseline FVm versus Paco(2) response slopes and Paco(2) measured postreperfusion were used to predict the FVm response to Paco(2) after reperfusion. The slopes were similar to those reported for anesthetized patients without liver disease. Predicted FVm exceeded measured FVm in 9 of the 10 patients. We conclude that mild hyperventilation prior to reperfusion of the graft liver prevents FVm increases above prereperfusion baseline level.