In supine humans the main drainage from the brain is through the internal jugular vein (IJV) but the vertebral veins (VV) become important during orthostatic stress because the IJV is partially collapsed. To identify the effect of this shift in venous drainage from the brain on the cerebral circulation, this study addressed both arterial and venous flow responses in the "anterior" and "posterior" parts of the brain when 9 healthy subjects (5 men) were seated and flow was manipulated by hyperventilation and inhalation of 6% carbon dioxide (CO2). From a supine to a seated position, both internal carotid artery (ICA) and IJV blood flow decreased (P=0.004 and P=0.002), while vertebral artery (VA) flow did not change (P=0.348) and VV flow increased (P=0.024). In both supine and seated positions the ICA response to manipulation of end-tidal CO2 tension was reflected in IJV (r=0.645 and r=0.790, P<0.001) and VV blood flow (r=0.771 and r=0.828, P<0.001). When seated the decrease in ICA blood flow did not affect venous outflow, but the decrease in IJV blood flow was associated with the increase in VV blood flow (r=0.479, P=0.044). In addition, the increase in VV blood flow when seated was reflected in VA blood flow (r=0.649, P=0.004) and the two flows were coupled during manipulation of the end-tidal CO2 tension (supine, r=0.551, P=0.004; seated, r=0.612, P<0001). These results support that VV compensates for the reduction in IJV blood flow when seated and that VV may influence VA blood flow.