The fine structure of the microvasculature in areas of focal cerebral ischemia was studied in squirrel monkeys and the changes in areas of impaired and unimpaired microvascular filling, as defined by carbon perfusion, were compared. Microcirculatory obstruction became evident three hours following middle cerebral artery (MCA) occlusion and appeared to be partly the result of compression of capillaries by perivascular glial swelling and developing cerebral edema. Slight endothelial swelling was a common finding. Intraluminal membrane-bound bodies were occasionally identified but they did not appear to be producing significant obstruction. The tight endothelial junctions remained intact and there was no evidence of accelerated micropinocytosis. Severe neuronal injury frequently preceded the development of the microvascular obstruction and was more widespread than the zones of impaired perfusion.