In experimental visceral leishmaniasis, euthymic but not athymic (nude) BALB/c mice respond to conventional treatment with pentavalent antimony, indicating that the in vivo efficacy of antimony is T cell dependent. This finding correlates with frequent antimony treatment failures for T-cell-deficient patients with visceral leishmaniasis. To determine whether the in vivo efficacies of alternative antileishmanial agents also require T cells, Leishmania donovani-infected euthymic and nude BALB/c mice were treated with pentamidine or amphotericin B. Pentamidine induced leishmanistatic activity in euthymic mice but had little effect in nude mice. In contrast, amphotericin B exerted potent leishmanicidal activities in both euthymic and nude animals. These results suggest that amphotericin B may be of particular use for T-cell-deficient patients with visceral leishmaniasis.