Occlusion of a middle cerebral artery is performed with a surgical clip which is placed through a transorbital approach. This results in a reproducible cerebral lesion (infarction) which was analyzed sequentially in a group of primates at intervals ranging from 2½ hours to 16 days. The earliest cytological alterations, involving neurons, neuropil and astrocytes, can be demonstrated convincingly 2½ hours after the arterial occlusion in paraffin-embedded sections, stained with hematoxylin and eosin. A detailed description of the topographic-cytologic abnormalities and the sequence of inflammatory changes elicited by this form of cerebral ischemia, as well as a delineation of the beginning of the post-ischemic healing processes are provided. A three-zone separation of the histological features is suggested. In addition, we illustrate the cellular alterations in the hemisphere opposite to the arterial occlusion and discuss the axonal changes observed in the different zones of the evolving ischemic encephalomalacia. Abnormalities in the microcirculation are also discussed.