Large doses of an ionic contrast medium (CM) can disrupt the blood brain barrier (BBB) osmotically. Acute hypertension (HT) also is known to open the BBB. We tested the hypothesis that these two factors potentiate each other in a rat model. Adult male Wistar rats, anesthetized with pentobarbital, underwent tracheostomy. An external carotid artery catheter was placed so that it opened into the patent common carotid artery; arterial blood pressure was recorded continuously. Of three groups of animals, two (HT) groups received metaraminol to elevate and maintain blood pressure in the range of 165 to 190 mm Hg. The third (normotensive) group received an equivalent volume of saline. Five minutes after injection of Evan's blue, either sodium/meglumine diatrizoate or saline was infused into the carotid cannula (2 mL in 30 seconds). Twenty minutes later the cardiovascular system was flushed with saline, and the brain was removed, frozen, and sectioned for gross and histofluorescent microscopic examination of BBB opening. The carotid injection of CM at a concentration of 1000 mosm/kg water did not produce gross evidence of BBB opening in the normotensive group. Similarly, hypertension at levels below 190 mm Hg did not produce gross evidence of opening in the carotid saline group. However, the combination of carotid CM and HT produced significant BBB opening. These results suggest that the risk factor of acute HT potentiates CM-induced BBB opening.