Cerebrovascular capacitance was tested by measuring local cerebral blood flow (LCBF) by xenon-contrasted CT scanning before and after the oral administration of 14.3 mg/kg of acetazolamide among 45 subjects including 15 age-matched controls without history of headache, 20 migraineurs with and without aura, 3 patients with cluster headache, and 7 patients with tension-type headache. Percentage increases of LCBF were measured in 10 regions located throughout both hemispheres. Laterality indices for asymmetric LCBF increases were calculated. Local cerebral blood flow in cortical gray matter increased 5.9% in controls, 9.9% in patients with tension headaches, but 18.6% in both migraine and cluster headache patients; significantly greater LCBF increases than among controls or among patients with tension headaches (P<0.05). Increases in LCBF were significantly asymmetric among migraine and cluster patients and provoked typical unilateral vascular headaches which responded to sumatriptan. Maximal asymmetric LCBF increases also corresponded to the reported side of the induced headaches confirming their vascular pathogenesis. Patients with tension headaches and controls without history of headache did not develop head pain after acetazolamide.