Thirteen dogs naturally infected with Leishmania infantum showing viscero-cutaneous signs of disease were treated with different dosages of liposomal amphotericin B (AmBisome). The animals were followed clinically and parasitologically over a period of eight months. Dogs which received three to five administrations of AmBisome 3-3.3 mg/kg showed rapid clinical improvement, with regression of lymphadenomegaly and splenomegaly, and cure of skin lesions. The clinical response was similar to that obtained with 14-21 doses of conventional antileishmanial drugs. However, follow-up lymph node aspirates remained positive for Leishmania in all dogs except one, which was treated with the total dose of AmBisome 15 mg/kg. The failure in parasitological cure may be due to inadequate drug targeting to parasitized cells, or to T-cell immune depression characteristic of patent cases of canine leishmaniasis, or to both.