To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.