In this article we describe an in vitro model for complement-dependent phagocytosis of liposomes. We have previously reported that complement-opsonized liposomes are avidly ingested by murine peritoneal or bone marrow-derived cultured macrophages. However, when the liposomes contained certain lipids, including phosphatidylinositol, ganglioside GM1, and sulfogalactosyl ceramide, that have been identified as causing prolonged circulation time in vivo, complement-dependent phagocytosis of the liposomes was greatly suppressed. We identify certain additional factors associated with suppressed complement-dependent phagocytosis, including, liposomal negative charge and liposomal prostaglandin E2 or thromboxane B2. Possible mechanisms responsible for suppression of complement dependent phagocytosis are suggested. We propose that suppression of complement-dependent phagocytosis could be a contributing factor in the promotion of increased circulation time of 'stealth' liposomes and that complement opsonization probably plays a role in vivo in removing liposomes from the circulation.