Interleukin 10 (IL-10), a suppressive Th2 cell-type cytokine, promotes disease progression in experimental visceral leishmaniasis. To extend testing the therapeutic effects of applying IL-10 receptor (IL-10R) blockade with antileishmanial chemotherapy, BALB/c mice with established intracellular Leishmania donovani infection were injected once with anti-IL-10R mAb at the time low-dose, daily pentavalent antimony (Sb) therapy was initiated. In this treatment model, simultaneous administration of anti-IL-10R enhanced overall antileishmanial activity in the liver in an interferon-gamma-dependent fashion, and accelerated the kinetics of Sb-associated killing, induced a >10-fold Sb dose-sparing effect and shortened the required duration of Sb treatment. These results suggest the possibility of using mAb-induced IL-10R blockade to develop low-dose and/or short-course immunochemotherapeutic regimens in visceral leishmaniasis.