To study the effect of a perfluorocarbon oxygen transport emulsion (Fluosol-DA) on reticuloendothelial system (RES) function, we measured the blood clearance of human erythrocytes transfused to rats. Compared with saline treatment, Fluosol-DA at 30 ml/kg doses significantly increased both the percent 20-hour blood recovery (mean 8.9% +/- 2.7 SEM vs 1.3% +/- 0.25 SEM) and 51Cr t1/2 survival (mean 14.0 hours +/- 2.7 SEM vs 3.5 hours +/- 0.33 SEM) of the human red cells. This suppression of RES clearance function was transient and no longer detectable seven days after single Fluosol-DA doses. The Fluosol-DA-induced RES block was about three times greater than that obtainable with 4 g/kg of a soybean oil emulsion used for clinical hyperalimentation. On the other hand, the effect of ethyl palmitate (0.5 g/kg), a potent but toxic RES blocker, was 3.5 times greater than that of Fluosol-DA in this test system. If Fluosol-DA also induces RES block in humans, this emulsion could be explored as a therapeutic RES blocker in certain immune cytopenias.