An electron microscopy study was conducted to investigate structural as well as functional changes of the blood-brain barrier in hepatic encephalopathy. Hepatic encephalopathy was induced in rats by two-stage hepatic devascularization producing ischemic liver damage. The permeability of the blood-brain barrier to lanthanum, horseradish peroxidase and [3H]inulin was determined, with electron microscopy performed on capillaries from different regions of rat brain. Marked swelling of the perivascular astroglial foot process and dilatation of extracellular spaces were observed in the cerebral cortex, pons, basal ganglia and cerebellar cortex in rats with acute hepatic failure. Diffusion of lanthanum and reaction products of horseradish peroxidase were completely restricted by intercellular tight junctions, but there was a significant increase in the amount of [3H]inulin leaking out of the capillaries in the cerebral cortex in rats with acute hepatic failure as compared with controls. [3H]inulin was found mainly in vesicles, vacuoles and endoplasmic reticulum. Our results indicate that brain edema in acute hepatic encephalopathy is mainly of the cytotoxic type and, to a lesser extent, of the vasogenic type, due to the increase of vascular permeability via the vesicle system.