This study was performed to evaluate whether increasing the permeability of the blood-brain barrier by unilateral intracarotid injection of hyperosmolar mannitol would alter O2 consumption and the O2 supply/consumption balance in the ipsilateral cortex. Rats were anesthetized with 1.4% isoflurane using mechanical ventilation. Retrograde catheterization of a unilateral external carotid artery was performed to administer 25% mannitol at a rate of 0.25 ml/kg/s for 30 s. The blood-brain barrier transfer coefficient (K(i) of 14C-alpha aminoisobutyric acid was measured in one group (N = 7) after administering mannitol. Regional cerebral blood flow (rCBF), regional arterial and venous O2 saturation and O2 consumption were measured in another group using a 14C-iodoantipyrine autoradiographic technique and microspectrophotometry (N = 7). Vital signs were similar before and after administering mannitol. K(i) was significantly higher in the ipsilateral cortex (IC) (22.3 +/- 8.4 microliters/g/min) than in the contralateral cortex (CC) (4.4 +/-1.1). rCBF was similar between the IC (105 +/- 21 ml/g/min) and the CC (93 +/- 20). Venous O2 saturation was lower in the IC (43 +/- 7%) than in the CC (55 +/- 4%). The coefficient of variation (100 x SD/mean) of venous O2 saturation was significantly elevated in the IC (32.3) compared with the CC (18.2), indicating increased heterogeneity of O2 supply/consumption balance. O2 consumption was higher in the IC (9.6 +/- 3.0 ml O2/100 g/min) than in the CC (6.7 +/- 1.5). Our data suggested that increasing permeability of the blood-brain barrier increased cerebral O2 consumption and the heterogeneity of local O2 supply/consumption balance.