Immune control of Trypanosoma cruzi, the causative agent of Chagas disease, requires the cytokine interferon- . The mechanism by which interferon- acts in control of infection is investigated here. Among the effector functions induced by interferon- is production of the microbicidal agent nitric oxide (NO) and other proteins that guide effector cells to sites of infection. While there is evidence to support a role for NO in control of T. cruzi infection, this study demonstrates that NO is not absolutely required for survival in T. cruzi infection. The increased production of certain cytokines by infected NO-deficient mice may compensate for the lack of NO and therefore contribute to the control of T. cruzi infection. Additionally, interferon- mediates recruitment of effector cells to infection sites by induction of chemokine ligands and chemokine receptors. In the absence of IFN- such recruitment is significantly delayed. Nitric oxide production and chemokine and chemokine receptor expression are part of a network of IFN- inducible responses that collectively contribute to the control T. cruzi infection.