The potential utility of neoglycoprotein conjugated multilamellar liposomes as macrophage specific drug delivery system was studied using hamycin as the model drug and visceral leishmaniasis as the model macrophage disease. Hamycin, a polyene antibiotic, was found to have a growth inhibitory effect on cultured Leishmania donovani promastigotes at a concentration of 0.05 microgram/ml. Hamycin entrapped in neoglycoprotein conjugated liposome (neohamysome) eliminated intracellular amastigotes of L. donovani in peritoneal macrophages 10 and 1.5 times more efficiently than did the free and liposome entrapped drug (hamysome), respectively. Moreover, neohamysome possibly could completely eliminate splenic intracellular parasites in a 45 day BALB/c mouse model of visceral leishmaniasis at a dose of 1.5 mg/Kg/day given for 4 consecutive days. Hamysome at a similar dose had 80% parasite suppressive effect whereas free drug could not be administered more than the dosage of 0.5 mg/Kg/day due to mortality problem. Neohamysome and hamysome were generally less toxic than the free drug as judged by erythrocyte lysis and several clinical parameters of liver toxicity. These results suggest a possible use of neoglycoprotein conjugated liposomes in macrophage-associated diseases.