Global hemispheric ischemia was produced in cats by bilateral carotid ligation and bleeding to a mean arterial pressure of 30± 2 (SE) mm Hg. Total electrocerebral silence, as determined by computer-based power analysis, was obtained and maintained for 15 minutes. After this severe cerebral ischemic episode, the heparinized blood was reinfused and the carotid clamps were removed. After the cerebral ischemia, the ventriculosubarachnoid space was perfused with an oxygenated fluorocarbon nutrient solution (OFNS) or modified Elliott's B solution (ES) (control perfusion). The OFNS perfusate contained 400 to 640 mm Hg pO2 (produced by means of a bubble oxygenator pump system) as well as electrolytes, glucose, and amino acids, all of which are known to be important in cerebral metabolism. Flow rates of the perfusion were maintained at either 3 or 6 ml/minute and intracranial pressures were never permitted to exceed 10 mm Hg. During passage through the ventriculosubarachnoid space, oxygen, carbon dioxide, and electrolytes were exchanged between the brain and the OFNS perfusate. In addition, the OFNS perfusate was capable of picking up pCO2, lactate, and pyruvate. This produced a significant return of electrocerebral activity (P < 0.01) and oxidative metabolism (P < 0.01), as evidenced by a decline in the lactate/pyruvate ratio in the OFNS-treated cats, but not in nonperfused animals or those perfused with ES. In this study the ventriculosubarachnoid system served as an alternate vascular tree and enabled the perfusate to accomplish many of the functions of blood. Substantial penetration of the perfusate products into the brain occurred, enabling oxidative metabolism, removal of waste products, and electrocerebral activity to be reestablished.