The sequential changes that occur during regeneration of cerebral microvessels was studied in young mice after a local freeze-injury. The immediate breakdown in the blood-brain barrier to horseradish peroxidase was followed by dissolution of cells in the vessel wall although the basal lamina was preserved. This residual basal lamina formed the pathway for the orderly regeneration of microvessels. Three days after injury, reactive endothelial cells with prominent pinocytosis and patent interendothelial channels were present at the edge of the lesion. By 5 days, endothelialization of necrotic vessels was in progress with patent vascular channels and tight junction formation. Establishment of astrocytic contacts or perivascular fibrosis by 7 days was generally followed by reconstitution of normal vascular morphology and integrity at 15 to 35 days after injury.