Perfluorochemical (PFC) emulsions have been examined for use as erythrocyte substitutes in the treatment of various disease states. The physiological changes induced by PFC infusion would be an important determinant of successful clinical therapy. Previous studies have reported PFC induced changes in the disposition of drugs. This report describes some physiological (hematology, cardiovascular, liver enzyme) changes resulting from a 30% blood exchange with a PFC emulsion in Beagle dogs. A 30% blood exchange with hydroxyethylstarch (HES) also was evaluated and compared to the PFC emulsion exchange. The blood pressure was markedly reduced shortly after PFC infusion while HES infusion produced only minor changes. Changes in the heart rate following blood replacement were similar for PFC and HES treated dogs. Hematology profiles also were similar for the PFC and HES treatment groups. The liver enzyme levels in PFC treated dogs showed marked elevations beginning shortly after PFC infusion and remained elevated for months after the initial PFC blood replacement. In contrast, HES treated dogs exhibited no observable changes in liver enzyme levels over the time course of the study.