The effects of osmotic opening of the blood-brain barrier (BBB) on local cerebral glucose utilization (LCGU) were studied in rats with the carbon 14-deoxyglucose method. The BBB was opened to Evans blue dye by unilateral carotid artery perfusion with hypertonic mannitol solution. (14C)-Deoxyglucose was injected 15 minutes or two to three hours later. Osmotic opening of the BBB resulted in focal areas of intense LCGU in affected areas of the perfused hemisphere. In the contralateral hemisphere, glucose utilization was diminished, especially in cerebral cortical areas. The effects were reversible. LCGU was normal in both hemispheres when permeability to Evans blue returned to normal two to three hours after carotid artery perfusion. In 3 of 5 experiments the administration of high doses of intravenous diazepam immediately following carotid artery perfusion with mannitol prevented an increase in LCGU in the perfused hemisphere but did not prevent lowering of LCGU in the contralateral hemisphere. Increased LCGU following osmotic opening of the BBB was not accompanied by a rise in local cerebral blood flow as measured by the iodoantipyrine method. Blood flow was, in fact, significantly decreased.