OBJECTIVE The vasomotor response can be tested by means of transcranial Doppler sonography. If a constant vessel diameter is assumed, the flow velocity changes will reflect blood flow volume changes. This hypothesis is difficult to verify. Simultaneous assessment of intracranial flow velocity and extracranial flow volume changes may solve this problem. METHODS We tested vasomotor response in 32 volunteers (age, 42+/-18 years) with 5% CO2. Acetazolamide (1 g) was tested in 15 volunteers (age, 28+/-8 years). To evaluate drug-dependent flow changes in the external carotid artery territory, acetazolamide was administered in 7 patients with unilateral occlusion of the internal carotid artery without evidence of collateralization through the ophthalmic artery (age, 67+/-12 years). Simultaneous recording included measurements of flow volume in the common carotid arteries (M-mode color duplex system) and flow velocity in the middle cerebral arteries. RESULTS With CO2 and acetazolamide, intracranial flow velocity increased by 31% and 39%, respectively, with a simultaneous increase of common carotid artery flow volume of 47% and 50%, respectively. No change in extracranial flow volume was observed in patients with an occluded internal carotid artery. CONCLUSIONS These data show not only the expected increase of flow velocity in the middle cerebral artery but also suggest an increase in cross-sectional vessel diameter of 6% and 4% with CO2 and acetazolamide, respectively. It remains unresolved whether this observation is due to a direct effect of the drug on the vessel walls or is simply pressure dependent.