An animal model for reversible blood-brain barrier disruption has been developed. Retrograde infusion of hypothermic saline solution (8 +/- 1 degrees C) into the left external carotid artery of normothermic, Wistar rats reversibly increases cerebrovascular permeability to Evans blue albumin in the left cerebral hemisphere. Isotonic saline solutions at 37 degrees C for Group I and at 8 +/- 1 degrees C for Group II were infused for 30 s at a constant rate of 0.12 ml/s into the left external carotid artery. Evans blue, the barrier tracer, was administered intravenously either prior to or at intervals 5, 30, 180, 360 min after the hypothermic saline infusion under pentobarbital anesthesia. All animals receiving hypothermic saline perfusion had disturbed blood-brain barrier permeability. Based on visual inspection, disruption grade in the left hemispheres of 10 of 16 animals was 3+. Mean values for Evans blue dye were found to be 0.32 +/- 0.08 mg% in left the hemisphere after normothermic saline infusion (Group 1), and 2.9 +/- 0.4 mg% in the same hemisphere after hypothermic saline infusion (Group II). The difference was found to be significant between Group I and Group II (P < 0.001). The increase in cerebrovascular permeability was temporary, however, although Evans blue albumin extravasion remained slightly elevated 3 h after infusion, it was normal 6 h after infusion.