After 180 min of temporary middle cerebral artery occlusion in rats, the affect of phenylephrine-induced hypertension on blood-brain barrier permeability was assessed. One of the following blood-pressure regimens was maintained during either a 30- or 120-min period of reperfusion: (a) 30/Norm, 30 min of normotensive reperfusion was allowed; (b) 30/HTN, mean arterial blood pressure was increased by 35 mm Hg during 30 min of reperfusion; (c) 120/Norm, 120 min of normotensive reperfusion was allowed; or (d) 120/HTN, mean arterial blood pressure was increased by 35 mm Hg during 120 min of reperfusion. Evans blue (30 mg/kg) was given, and brains were analyzed for Evans blue by spectrophotometry. Evans blue (microgram/g brain tissue, mean +/- SD) was greater (P less than 0.05) in both hypertensive groups versus their time matched normotensive groups (30/HTN: 80 +/- 16 versus 18 +/- 6 in the 30/Norm group; 120/HTN: 17 +/- 6 versus 8 +/- 3 in the 120/Norm group). In addition, Evans blue was greater (P less than 0.05) in both 30-min groups versus their pressure matched 120-min groups (30/Norm: 18 +/- 6 versus 8 +/- 3 in the 120/Norm group; 30/HTN: 80 +/- 16 versus 17 +/- 6 in the 120/HTN group). The data are consistent with previous studies which have demonstrated an opening of the blood-brain barrier at the onset of reperfusion. In addition, the data support a hypothesis that changes in blood-brain barrier permeability are more sensitive to hypertension in the early period of reperfusion.