The pattern of Evans blue extravasation in the brain in norepinephrine-induced acute hypertension is similar to our previous observations using horseradish peroxidase as a tracer. Pretreatment with flunarizine IV resulted in significant reduction of RISA leakage in all regions of the brains of acutely hypertensive rats. The reduction in RISA leakage in the drug-treated hypertensive group is not attributable to differences in the blood pressure elevations which were not significantly different in both groups. These studies suggest a role for calcium in the increased endothelial permeability occurring in cerebral vessels in acute hypertension. Further morphological studies are required to determine whether flunarizine reduces permeability by decreasing pinocytosis.