Unilateral locus ceruleus lesion enhances leakage of radioiodinated human serum albumin into the ipsilateral cerebral cortex of rats with norepinephrine-induced hypertension. This ultrastructural study was undertaken, to determine the mechanism by which this permeability alteration occurs, using horseradish peroxidase (HRP) as a tracer. Unilateral locus ceruleus lesion was produced in male Wistar-Furth rats by stereotaxic microinfusion of 5 micrograms of 6-hydroxydopamine. Two weeks later, rats were injected with HRP intravenously and acute hypertension was induced in awake rats by an intravenous infusion of norepinephrine (6 micrograms), epinephrine (6 micrograms) or angiotensin amide (12 micrograms) given over a 2-min period. Thirty seconds later, the rats were perfused with fixative under deep anesthesia and their brains were sliced and processed for demonstration of HRP reaction product. Leakage of HRP occurred in both cerebral hemispheres in response to hypertension induced by the three pressor agents, but the leakage was greater on the lesioned side in response to epinephrine and norepinephrine, while in the case of angiotensin-induced hypertension side-to-side differences in permeability alterations were not observed. In both cerebral hemispheres increased permeability affected mainly arterioles, which showed enhanced pinocytosis as the principal mechanism of HRP extravasation.