Although short-course therapy with new lipid formulations of amphotericin B represents an advance over lengthy traditional treatments in visceral leishmaniasis (kala-azar), high cost has rendered these agents largely irrelevant in developing countries where the disease is endemic. Therefore, we tested standard amphotericin B deoxycholate mixed with a commercial fat emulsion as short-course treatment for Indian visceral leishmaniasis in Bihar in 1997/98. Seventy children and adults with splenic aspirate-documented infection, 23 of whom had failed prior antimony (Sb) therapy, received 5 alternate-day infusions of 2 mg/kg. Apparent cure, which required a parasite-free splenic aspirate smear, was assessed 20 days after treatment (day 30); definitive cure was determined at 6 months. Other than anticipated infusion-related fever and/or chills, treatment was safe and well tolerated. One patient required dose modification because of mild, reversible renal insufficiency. Sixty-nine patients (98.6%, CI 92.3-100%) had apparent cures; during follow-up, there were 4 treatment failures (relapses, 3; unrelated death, 1), yielding definitive cures in 65 of 70 patients (92.9%, CI 84.1-97.6%). Including retreatment costs for patients in Bihar (who now often fail initial Sb therapy), the final per patient cost of the tested regimen (US $260) was 59% and 43% less than treatment with Sb or conventional amphotericin B alone, respectively. Short-course treatment with amphotericin B-fat emulsion is active, cost-effective treatment for patients with visceral leishmaniasis including those with Sb-unresponsive infection.