Previous studies have shown that hepatic phagocytosis of red blood cell (RBC) stroma can depress reticuloendothelial system (RES) phagocytic function and increase susceptibility to shock. Since the RBC stroma used in these experiments contained substantial amounts of adherent hemoglobin, the present study was carried out to evaluate the role of the hepatic uptake of RBC membrane material on RES phagocytic function and susceptibility to endotoxin shock in rats. Neuraminidase-treated RBC which contained normal amounts of hemoglobin and RBC ghosts which were hemoglobin-free were used. Both preparations were removed from the circulation primarily by the liver. RES phagocytic function was depressed following the hepatic uptake of 29 X 10(8) neuraminidase-treated RBC and 26 X 10(8) RBC ghosts. RES uptake of neuraminidase-treated RBC was associated with an increase in susceptibility to endotoxin shock, but RBC ghosts did not affect shock susceptibility. Thus, RBC ghosts and intact RBC are equally effective in depressing RES phagocytic function, but RBC ghosts did not affect susceptibility to endotoxin shock.