The study was undertaken to investigate the contribution of B cells, Th1/ Th2 subsets of CD4+ and Tc1/Tc2 subsets of CD8+ T cells to control of Trypanosoma cruzi infection in mice. B cell deficient mice exhibited a delay in parasitemia and an extended time to death relative to mice lacking CD8+ T cells. But, both B cell- and CD8+ T cell-deficient mice succumbed to the infection, suggesting the requirement of an antibody and a CD8+T cell response for control of T. cruzi. To investigate the role of Th1 and Th2 subsets of CD4+ T cells in determining the outcome of T. cruzi infection in mice, we developed T. cruzi clones that express ovalbumin (OVA) and used OVA-specific Th1 and Th2 cells. Mice receiving OVA-specific Th1 cells and then challenged with OVA- expressing T. cruzi G-OVA.GPI showed significantly lower parasitemia and increased survival in comparison to mice that received no cells or Th2 cell recipients that developed higher parasitemias, exhibited higher tissue parasitism and inflammation and higher. Mice receiving a mixture of both Th1 and Th2 OVA-specific cells were also not protected from lethal challenge. OVA-specific Tc1 and Tc2 cells were also assayed for their ability to protect mice during infection with OVA-expressing T. cruzi. Mice receiving OVAspecific Tc1 or Tc2 cells developed lower parasitemia and tissue parasitism and survived a normally lethal infection with OVA-expressing T. cruzi GOVA.GPI. In contrast, mice receiving no cells, Tc1 cells or Tc2 cells but infected with wild-type T. cruzi developed significantly higher blood and tissue parasite burdens and succumbed to the infection. Tc1 cells continued to make primarily IFN-(c) ?but the Tc2 population failed to retain a type 2 cytokine production pattern and instead exhibited predominantly a type 1 pattern of cytokine production in vivo. Tc1 or Tc2 populations incapable of producing IFN-(c) ?were unable to provide protection to infection with OVA- expressing T. cruzi suggesting that Tc1 cell-mediated protection in mice against lethal T. cruzi GOVA.GPI was dependent on the production of IFN-(c) ?by these cells.