This study was performed to investigate whether a fraction of hydroxyethyl starch macromolecules, prepared from pentastarch and known as "Hes-Pz," with molecular weights of 100,000-1,000,000, protects against blood-brain barrier (BBB) disruption due to intracarotid injection of hyperosmolar mannitol. Rats were anesthetized with isoflurane, and retrograde catheterization of a unilateral eternal carotid artery was performed. Except for the Control group (n = 8), hemodilution was performed using lactated Ringer's solution LR group, n = 7), 6% hetastarch (HES group, n = 7), or 6% HES-Pz (HES-Pz group, n = 8) to reduce the hematocrit to about 23%. The BBB transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid was determined after a unilateral intracarotid injection of 25% mannitol. Blood pressure and hematocrit were similar in all groups. In the control group, Ki was increased significantly in the ipsilateral cortex (IC) where mannitol was injected (16.3 +/- 6.1 vs 4.1 +/- 1.4 microL.min-1) when compared with the contralateral cortex (CC). Ki was similar in the CC in all four groups. The Ki in the IC was significantly lower in the HES-Pz(6.4 +/- 3.5 microL.g-1.min-1) than in the Control, HES, or LR group (16.3 +/- 6.1, 19.0 +/- 12.9, 17.9 +/- 10.8 microL.g-1.min-1, respectively). Our data suggest that HES-Pz significantly attenuates disruption of the BBB caused by an injection of hyperosmolar mannitol.