The left middle cerebral artery and both carotid arteries of 17 cats were occluded to evaluate the effects of oxygenated fluorocarbon emulsion on brain ischemia. Carotid and middle cerebral arteries were occluded concurrently for 2 hours, followed by occlusion of the middle cerebral artery only for another 24 hours. Six animals were treated with oxygenated fluorocarbon emulsion delivered by ventriculocisternal perfusion, 5 received ventriculocisternal perfusion with mock cerebrospinal fluid, and 6 were untreated. Perfusions were started 3 hours after the initial ischemic insult. Infarct size judged by tetrazolium staining and standard neuropathological stains was significantly smaller in the treated animals. The mechanism of protection is as yet unknown, but most likely reflects oxygen/nutrient diffusion into the ischemic middle cerebral artery zone from the ventricular fluorocarbon, or removal of harmful metabolites. The results imply that ventriculocisternal perfusion with fluorocarbon emulsion can preserve neuronal function during a major cerebral vessel occlusion. In the cat, therapy is effective if begun within 3 hours after ischemia starts.