This study was designed to determine the contribution of elevated plasma ammonia levels to blood-brain barrier (BBB) abnormalities in the presence of intact liver. The permeability changes of the BBB were investigated grossly with Evans blue (EB) and quantitatively by measuring the blood-to-brain transfer content for α-aminoisobutyric acid (AIB) in normal rats and rats subjected to sublethal doses of ammonium acetate (NH₄OAc) (750 and 600 mg/kg ip; at 30-min intervals). Some rats were pretreated with dexamethasone (DXN). Injection of NH₄OAc increased both plasma and brain ammonia concentrations about 16- and 5-fold, respectively, above the control level. In rats receiving NH₄OAc injection, the blood-to-brain transfer constant (K _i) for AIB was increased 3-to 11-fold. The elevatedK _i values were limited to certain gray matter areas and less pronounced permeability changes were detected in white matter. Extravasation sites of EB were more restricted and were especially observed in thalamus and cerebellum, whereas cortex and white matter were unaffected. Dexamethasone pretreatment for 3d reduced both leakage of EB and theK _i for AIB in NH₄OAc injected animals, whereas acute treatment appeared ineffective. Dexamethasone did not prevent the development of coma but slightly decreased the ammonia concentration in plasma and brain. The results obtained indicate that hyperammonemia may disrupt BBB integrity not only to AIB and EB but also enhance the transport of other solutes.