Mechanical fragility measurements have been made in vitro on fluorocarbon emulsions mixed with normal and sickle cells in plasma to determine the effect of fluorocarbon. Emulsions of FC-80 with Pluronic F-68 were added to give final solutions of 0, 1, 5, 10, and 20% fluorocarbon emulsion. The effect of the fluorocarbon emulsion was observed in the presence and absence of oxygen. In the presence of oxygen, there was no effect of the fluorocarbon emulsion on the mechanical fragility of normal or sickle cells. In deoxygenated systems, however, there was significantly less hemoglobin in the plasma during the mechanical fragility test with fluorocarbon emulsion added to sickle cell blood. The normal blood was not affected by the fluorocarbon emulsion in the deoxygenated system. Five percent of fluorocarbon emulsion was required for a significant effect on the deoxygenated sickle cells. Since the effect of the fluorocarbon emulsion was in a deoxygenated condition, the effect is due to the presence of the fluorocarbon emulsion and not its oxygen carrying capability.