To determine if cytokine immunotherapy accelerates the response to conventional treatment in visceral leishmaniasis (kala-azar), previously untreated Indian patients were given antimony for 30 days (n = 15) or antimony plus interferon-gamma (IFN-gamma; n = 16). After 10 days, 10 (63%) of 16 patients treated with antimony plus IFN-gamma versus 1 (7%) of 15 randomized to antimony alone were considered cured of parasites (P < .005). On day 20, 14 (93%) of 15 versus 6 (40%) of 15 patients, respectively, were apparent clinical cures (P < .006), and treatment was discontinued early in the 14 IFN-gamma treated responders. Day 30 apparent cure rates (100% vs. 73%) and 6-month ultimate cure responses (87% vs. 60%) were higher in IFN-gamma-treated patients but not statistically different from controls (P > .05). All 13 IFN-gamma-treated subjects who were cured (12 of whom received therapy for 20 days) have remained healthy with follow-up of 14-24 months (mean, 18.9). These results indicate that IFN-gamma successfully accelerates the parasitologic and clinical response to antimony treatment, an effect that should permit shortening the duration of conventional therapy in previously untreated kala-azar.