Dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Ch) liposomes containing a soybean-derived sterylglucoside mixture (SG) (SG-liposomes) are effective for targeting hepatocytes in mice. We investigated uptake of SG-liposomes to hepatocytes compared with that via the galactose receptor. The association of SG-liposomes entrapping calcein was examined at 4 degrees C or 37 degrees C, changing incubation time and the SG concentration of the liposomes, and using the inhibitor on the galactose receptor in rat primary cultured hepatocytes. The amount of liposomes recovered with hepatocytes was determined by measuring the concentration of calcein and imaged with confocal laser scanning microscopy in the cultured cells. The association of SG-liposomes at 4 degrees C was significantly decreased compared with that at 37 degrees C as that of liposomes containing lactosylceramide (LC) (LC-liposomes) that were already known to be taken up by hepatocytes via the asialoglycoprotein receptor. While the association of SG-liposomes at both 4 degrees C and 37 degrees C increased with the increase of incubation time, the association of SG-liposomes at 37 degrees C was almost saturated after 1 h. The association of SG-liposomes pretreated with concanavalin A was significantly decreased (to about 40% of that without pretreatment at 37 degrees C) and was at the same level as the association of SG-liposomes and non-SG-liposomes at 4 degrees C. The association of the SG-liposomes by hepatocytes incubated for I h at 37 degrees C was almost saturated at about 2.0 nmol SG/mg protein. The association of the SG-liposomes with hepatocytes was not inhibited in the presence of LC-liposomes. The affinity of the galactose residue for hepatocytes appeared to be similar to that of the glucose residue in the liposomes, because the amount of sugar residue and the association of SG-liposomes and LC-liposomes were almost the same values. These results suggest that SG-liposomes may be associated with hepatocytes not by a galactose receptor-mediated endocytosis.