Artificial blood substitutes have been prepared with liquid fluorocarbons, Pluronic polyols, hydroxyethyl starch, electrolytes, and bicarbonate buffer. Dispersing the fluorocarbons is by sonication in the presence of the polyols. A CO-2 atmosphere is provided to prevent the formation of fluoride ions which otherwise form. Viscosity, oncotic pressure, osmotic pressure, and pH are adjusted to that of rat blood. With such preparations all of the normal blood of rats can be replaced. Such animals survive, carry out usual functions, regenerate blood cells and plasma protein, and continue to grow and develop. Volumes up to 30 times the blood volume of the rat have been perfused. Perfluorotributylamine has been the most successful of the fluorocarbons, in spite of its prolonged retention in the tissues, but progress has been made with the perfluorodecalins which leave the tissues rapidly. "Bloodless" rats show no reaction to dextran which ordinarily causes acute hypersensitivity reactions in normal rats. Rabbit antirat serum, which has little effect on normal rats, is toxic to "bloodless" rats. Lack of circulating enzymes in "bloodless" rats. Lack of circulating enzymes in "bloodless" rats allows a) specific enzymes to be given to achieve the enzyme profile desired; and b) enzyme-labile compounds to be kept in circulation. "Bloodless" rats made possible by artificial blood substitutes afford a new biomedical research tool.