Complications of amphotericin B limit its wide application in the treatment of patients with kala-azar. This study was undertaken with an aim to minimize anti-renal complications and severe rigor in course of treatment with this drug. Parasitologically confirmed kala-azar cases (n = 230) were randomized equally into two groups: a control group received amphotericin B only at a dose of 1 mg/kg of body weight/day for 20 days and a patient (test) group received 500 mL of physiologic saline and 30 mL (60 meq/L) of KC1 with amphotericin B. We observed a significantly lower increase in serum creatinine levels (P = 0.0001) and a lower incidence of severe rigor and fever (P = 0.0165) in the test group than in the control group. However, the ultimate cure rate was not significantly different (P = 0.5637) between two groups after 12 months of follow-up. Relapses occurred after even after six months in both groups. Persons with relapses were treated with 25 infusions of amphotericin B and cured. Supplementation of amphotericin B with 500 mL of physiologic saline and 30 mL (60 meq/L) of KCl during treatment could help prevent an increase in serum creatinine levels and severe rigor and would make the treatment of kala-azar with amphotericin B easier.