Phagocytosis by adherent human monocytes of human erythrocytes (RBC), sulfatide-enriched by incubation with 10(-12) to 10(-9) M cerebroside sulfate, was enhanced approx. 6-fold. Increased phagocytosis was observed only in RBC opsonized with fresh plasma, and not in non-opsonized or serum-opsonized RBC. Increased phagocytosis was immunoglobulin- and complement independent. Thrombospondin and von Willebrand factor, present in plasma but not in serum, and binding selectively to sulfatides, are likely mediators of the enhanced phagocytosis.