We recently reported the preparation and in vitro targeting of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs) [Viroonchatapan et al. Pharm. Res. 12 1176-1183 (1995)]. The current study was designed to determine whether these novel liposomes can be targeted to the mouse liver with the aid of an extracorporeal magnet. An on-line liver perfusion system consisting primarily of a sample injector, permanent magnets, and a fluorescence detector was established for a real-time measurement of targeting efficiency of TMs containing calcein as a fluorescent marker. Normal and reticuloendothelial system (RES)-blocked livers from mice were used for the perfusion experiments. In the RES-blocked livers, percentage holdings of TMs were 73-80% and 26-45% in the presence and absence of magnetic field, respectively, indicating an efficient targeting of TMs with a targeting advantage index (TAI) of 1.6-3.1. On the other hand, TAI in the normal livers was found to be 1.1-1.4 and less than that in the RES-blocked livers, suggesting a role of RES uptake of TMs. The effects of DM concentrations in TM suspensions on the percentage holding of TMs were shown to be minor. Liposome concentration dependence was observed for hepatic uptake of TMs, possibly because of the saturation of phagocytosis by Kupffer cells. The present results suggest that TMs would be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.