Perfluorocarbon blood substitutes have been shown to exert a protective effect in animal models of cerebral ischemia. The mechanisms by which PFCs improve cerebral hemodynamics are uncertain, however decreased viscosity, small particle size and high oxygen solubility relative to plasma are important factors. Extensive perfluorocarbon exchange transfusion (FC-43) in the rat to a hematocrit of 1%, produces a 100% increase in total cerebral blood flow (FIO2 = 1.0, CaO2 = 6 vol%). Similar increases were seen in normal blood circulated animals breathing 12% O2 (CaO2 = 12 vol%). Therefore, immediately following PFC exchange and the resulting decrease in CaO2, oxygen delivery to the brain is maintained by increasing total blood flow in a manner similar to hypoxic hypoxia.