Oxygen-carrying perfluorochemical emulsions may become useful for transfusions when red cells cannot be used. Since accumulation of perfluorochemicals in reticuloendothelial cells has been demonstrated, we tested the phagocytic function of monocytes and neutrophils in rabbit and human blood exposed in vivo and in vitro, respectively, to perfluorotributylamine (Oxypherol) a perfluorochemical blood substitute. Neutrophil and monocyte phagocytosis was assessed by determining the uptake of serum-coated fluorescent beads by monocytes and neutrophils in whole blood. Morphologic changes were assessed by electron microscopy. The phagocytic activity of monocytes and neutrophils in the blood of four rabbits injected 4 hours earlier with 70 to 85 ml of Oxypherol (28 ml/kg) was depressed by 87 +/- 1.0 percent. Neutrophils in this blood showed morphological alterations characterized by swelling and extensive vacuole formation. Similar changes were found in neutrophils and monocytes of human blood incubated with Oxypherol (10-50%, V/V) at 37 degrees C for 1 hour. The phagocytic activity of human neutrophils and monocytes exposed to 20 percent, V/V Oxypherol was depressed by 35 +/- 9.9 percent. We conclude that caution should be exercised when administering perfluorochemical blood substitutes in patients exposed or at risk of infection.