The authors investigated the influence of variations in global cerebral blood flow (gCBF) on regional flow changes during visual stimulation. Global flow was varied using different end-expiratory CO2 values (PETCO2) between 20 and 70 mm Hg. Visual stimulation was performed with a red LED-array flashing at 8 Hz. Blood flow was measured with 0-15-butanol, continuous arterial blood sampling, and positron emission tomography (PET). Global flow changes surpassed the published values of O-15-H2O studies, better fitting the results of the inert gas technique (gCBF at 20, 40, and 70 mm Hg PETCO2 +/- SD was 31 +/- 4, 48 +/- 13, and 160 +/- 50 mL 100 g(-1) min(-1), respectively). The relation between PETCO2 and CBF in the current study was best described by an exponential rather than a linear function. At low PETCO2, the activation-induced flow changes are moderately damped, whereas at high PETCO2, they are nearly lost (deltaCBF (+/-SD): 52% +/- 25%, 68% +/- 22%, 16% +/- 25% at PETCO2 = 20, 40, 70 mm Hg, respectively).