The reference treatment in visceral leishmaniasis is administration of antimonial compounds (Pentostam, Glucantime). Primary and secondary failures have been reported and may involve several mechanisms resulting in alterations in the T-cell-dependent response, particularly in HIV-positive patients. Alternative agents proposed for use as single-drug therapy or in combination with other drugs include Lomidine, which carries a high risk of toxicity, allopurinol, cytokines (IL-2 and interferon gamma), and amphotericin B. Amphotericin B, in addition to effects on the metabolism of sterols in the wall of the protozoan, induces macrophage activation. This article illustrates the difficulty of treatment of visceral leishmaniasis by reporting the case of an immunocompetent 36-year-old patient whose bone marrow cultures remained positive after successive treatment, over 48 months, with two courses of Glucantime (60 mg/kg/day for 15 days), one course of allopurinol (10 mg/kg/4 weeks), two courses of Glucantime in combination with interferon gamma, splenectomy, and one course of Pentostam (20 mg/kg/4 weeks). Bone marrow cultures became negative after administration of amphotericin B (1 mg/kg every 48 hours for 8 weeks). Cytokine studies disclosed defective production of IL-2, IL-1 beta, and IFN gamma. Amphotericin B seems to be a valuable alternative when conventional treatment fails. The liposomal form is especially promising.