Blood-brain barrier permeability was investigated in acute focal ischemia after MCA occlusion and reperfusion. Four kind of tracers were used: sodium fluorescein and ionic lanthanum as a small molecular tracer, and Evans blue and HRP as a macromolecular tracer. BBB permeability to the tracers was observed macroscopically and studied by electron microscopy. The MCA was dissected free and occluded by ligation with 10-0 monofilament nylon suture. In the reperfusion model, the nylon suture was cut and the occluded MCA was reopened. Diffuse fluorescein staining was noted in the ipsilateral cortex; however, there was no extravasation of Evans blue or HRP in the occlusion model. Ionic lanthanum was demonstrated in the interendothelial space, basement membrane, and extracellular space. In the reperfusion model, intense fluorescein staining and hemorrhagic infarction were observed. Remarkable extravasation of Evans blue and HRP was also revealed in the ischemic lesion. HRP was demonstrated in the basement membrane and around the neuropils. Ultrastructural findings suggested that small molecules such as sodium fluorescein and ionic lanthanum may pass through the entire interendothelial cleft into the extracellular space before leakage of the macromolecules in the acute ischemic stage. Between 30 to 60 min after MCA occlusion, cerebral edema may begin with an escape of water and ions through the tight junctions. Reperfusion of MCA in the acute stage of ischemia may lead to abnormal vascular permeability to macromolecules as a manifestation of severe damage to the BBB.