The microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during infection with Leishmania or Trypanosoma cruzi.  However, we have found that mice deficient in nitric oxide synthase 2 (NOS2-/-) are less susceptible to infection with L. major than mice deficient in IFN-g (GKO), suggesting that there is an IFN-g dependent but NOS2 independent mechanism of resistance to this parasite.  In order to investigate this issue, we infected NADPH phagocyte oxydase deficient mice (gp91phox -/-) with L. major or T. cruzi and followed the course of infection.  We found that the course of infection in gp91phox-/- mice did not differ significantly from the course of infection in wild-type mice. In contrast, when infected gp91phox-/- mice with T. cruzi all mice succumbed to infection between day 15 and 21, while wild-type mice did not. Interestingly, gp91phox-/- mice have similar or reduced parasitemia and similar levels of IFN-g and TNF in serum and spleen cell culture supernatant when compared to wild-type controls. Further investigation demonstrated increased serum levels of NO_x at day 15 of infection. The association between this free reactive nitrogen species and mortality is under investigation, but we speculate that the high levels of NO in sera of p91phox-/- mice induce tissue damage and shock.  This issue is currently under investigation.