Recently we reported that serum contains opsonins specific for hepatic and splenic phagocytic cells and that these opsonins have different properties and affinities for cholesterol-rich and cholesterol-free egg phosphatidylcholine liposomes (Moghimi, S.M. and Patel, H.M. (1988) FEBS Lett. 233, 143-147). In the present report we investigate the affinity of these opsonins for the liposomes prepared from sphingomyelin and saturated phospholipids, as measured by their effect on the uptake of these liposomes by hepatic and splenic phagocytic cells. Results presented here suggest that neither liver- nor spleen-specific opsonins have affinity for sphingomyelin or saturated phospholipid liposomes since serum fails to enhance their uptake in liver or splenic cells. On the contrary, these liposomes attract serum dysopsonins which inhibit their uptake by liver cells. Inclusion of cholesterol in these liposome preparations enhances their uptake in splenic cells but not in liver cells. It is suggested that fluidity and hydrophobicity of liposomal membranes play an important role in attracting the right opsonins which determine their phagocytic fate.