The potential feasibility of using exogenously administered human interferon for the treatment of selected cases of leishmaniasis prompted us to study the effects of murine interferon on the course of Leishmania tropica infection in C57Bl/6 mice. L cell-derived mouse interferon was administered daily by intraperitoneal (1,000 and 10,000 U) or intralesional (100 U) injection in mice inoculated into footpads with L. tropica amastigotes. Footpad swelling and tissue parasite density were assessed over the course of infection. Interferon treatment did not significantly affect these clinical and parasitological parameters. Furthermore, addition of interferon (100–100,000 U) to cultures of amastigote-infected mouse peritoneal macrophages or to axenic cultures of promastigotes did not affect replication. We conclude that interferon lacks intrinsic antileishmanial activity and does not significantly enhance host defense against Leishmania.