SUMMARY Disruption of the blood-brain barrier (BBB) daring acutehypertension may contribute to hypertensive encephailopathy. In this study we tested the hypothesis that, in chronic hypertension, vascular changes might influence the susceptibility of the BBB to disruption. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), 3-4 months of age, were anesthetized and acute hypertension was produced by infusing phenylephrine intravenously (i.v.). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected i.v. The ratio of brain-to-blood RISA was used as an index of permeability of the BBB expressed as protein transfer. In both SHR and WKY at resting arterial pressure, the protein transfer was< 0.10%. In WKY exposed to acute hypertension (mean arterial pressure increased by 87 ± 7 mm Hg), the protein transfer was 2.77 ± 0.60%. In SHR with acute hypertension superimposed on chronic hypertension (arterial pressure increased by 80 ± 7 mm Hg), the protein transfer was 1.16 ± 0.45% (p< 0.05, SHR vs WKY). These data suggest that cerebral vessels are less susceptible to disruption of the BBB by acute hypertension in SHR than in WKY. We speculate that the finding of reduced susceptibility to BBB disruption in chronic hypertension may explain, in part, the apparent susceptibility of previously normotensive patients to acute hypertensive encephalopathy.