This study investigates the use of [(99m)Tc] liposomes for the detection of sentinel lymph nodes. A variety of [(99m)Tc] liposome formulations were compared with common lymphoscintigraphic agents including [(99m)Tc] regular-sulfur colloid (SC), [(99m)Tc] 0.22 microfiltered-SC, [(99m)Tc] reduced heating time 0.22 microfiltered-SC, and [(99m)Tc] human serum albumin (HSA) in rabbits. Images were acquired for the first 60 minutes and at 24 hours, followed by tissue biodistribution study. All agents except [(99m)Tc] regular SC demonstrated good migration from the injection site. Agents were retained in the popliteal node at 24 hours to varying degrees as follows: both [(99m)Tc] filtered SC preparations > [(99m)Tc] regular SC > [(99m)Tc] liposomes > [(99m)Tc] HSA. [(99m)Tc] liposome imaging can be used to develop novel liposome compositions with improved lymph node diagnostic and drug delivery characteristics.