UNLABELLED This study was performed to evaluate whether morphine could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmolar mannitol. Under isoflurane anesthesia, rats in a control group were infused with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid. Infusion of morphine 3 mg/kg in the small-dose morphine group and 10 mg/kg in the large-dose morphine group was completed, 10 min before administering mannitol. There were no statistical differences in systemic blood pressures between these three groups of animals. In the control group, the Ki of the ipsilateral cortex where mannitol was injected, increased to 4.6 times that of the contralateral cortex (19.5 +/- 8.5 vs 4.2 +/- 1.2 microL. g(-1). min(-1), P < 0.002). The Ki of the ipsilateral cortex of the small-dose morphine group was 13.5 +/- 7.6 microL. g(-1). min(-1). The Ki of the ipsilateral cortex of the large-dose morphine group was 9.2 +/- 4.5 microL. g(-1). min(-1) and was smaller than that of control animals (P < 0.05). There was no significant difference in the Ki of the contralateral cortex among the three groups. In conclusion, morphine attenuated BBB disruption induced by hyperosmolar solution without significant effects on systemic blood pressure. IMPLICATIONS Our study suggests that morphine may be effective in reducing the blood-brain barrier disruption by hyperosmolar mannitol without significant effects on systemic blood pressure.