Amyloid plaques and neuronal loss with reactive gliosis are hallmarks of Alzheimer's disease (AD). The amyloid deposits are composed of β-amyloid peptide (βA), which is considered to be causal factor of AD, although the mechanisms by which it induce neurodegeneration are still unknown. Such a role is strongly supported by transgenic mice that overexpressed βA production. The origin of βA in brain parenchyma and vessels of AD patients is not known. We examined pattern of vascular βA permeability by open blood-brain barrier (BBB) induced by global cerebral ischemia (GCI). Rats underwent single or repeated GCI followed by i.v. injections of human synthetic βA. βA was given 3 times a week during a three month survival period after single or repeated GCI. Postischemic βA-injected rats demonstrated multifocal and widespread βA extravasation in hippocampus, cerebral cortex and occasionally in white matter. βA extravasation involved arterioles, veins and vonules. Neuronal glial and pericyte bodies were observed filled with βA. For the first time direct evidence is provided that soluble human βA crosses the open BBB and can arise in brain from circulation. The pathology of the rats brain is striking. As in AD, there are irregular diffuse amyloid plaques, neuronal loss and reactive gliosis. This pathology appears to have similar distribution as in AD, hippocampal and cortical changes being most severe. This results could help, both in understanding the relationships of the various aspects of the AD pathology and in testing therapeutic approaches based upon these relationships.