Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.