We designed a new model for studies on atherogenesis in cerebrovascular systems. Myointimal thickening in the rabbit cerebral arteries was induced following intimal injury produced by a silicone rubber cylinder with nylon thread and which was injected from the bifurcation of the right external and internal carotid arteries to embolize either the intracranial internal carotid or middle cerebral artery. Fifteen minutes after the cylinder had been removed, there was a denudation of the endothelium, and platelets adhered to the exposed subendothelium at the site of embolization of the cylinder. Within 3 days, this denuded surface was completely covered by regenerated endothelial cells, and intimal thickening was not observed. After 7 and 28 days, there was a striking myointimal thickening composed of smooth muscle cells in the fibroelastic stroma in the injured region. Permeability of the regenerated endothelium to horseradish peroxidase continued to be enhanced through the intercellular junctions and by increase of vesicular transport after the regenerated endothelial cells had completely covered the denuded area. These findings suggest that enhancement of permeability of plasma constituents of the regenerated endothelium plays an important role in the atherogenesis of cerebral arteries.