Patients do not always respond to treatment of visceral leishmaniasis with pentavalent antimony, and the drug has toxic effects. Amphotericin B might be useful as an alternative first-line treatment for the disease. We compared the efficacy of amphotericin and sodium stibogluconate in a prospective randomised trial in 80 uncomplicated and parasitologically confirmed cases of Indian kala-azar. None of the patients had received an antileishmanial agent before. Sodium stibogluconate was given at 20 mg/kg in two divided doses daily for 40 days, and amphotericin in fourteen doses of 0.5 mg/kg infused in 5% dextrose on alternate days. All 40 patients randomised to amphotericin were cured; of the 40 patients assigned to sodium stibogluconate, 28 (70%) showed initial cure and 25 (62.5%) showed definitive cure (p < 0.001). With amphotericin, there was quicker abatement of fever and more complete spleen regression with no serious adverse effects. Amphotericin is effective in the first-line treatment of Indian kala-azar and superior to antimony therapy.