Trypanosoma cruzi-infected mice show disturbance in the peripheral immune system such as polyclonal lymphocyte activation, autoantibody production, and immunosuppression of T lymphocytes. Previous observations in our laboratory showed that some stocks of T. cruzi can be contaminated with mouse hepatitis virus type 3 (MHV-3). Literature has shown that MHV-3 infection induces immunologic disorders characterized by thymic involution with marked cell depletion. However, the effects of interactions between MHV-3 and the parasite on the immune system are not well understood. In the present study specific-pathogen-free CBA mice were inoculated with MHV-3, alone or associated with different stocks of T. cruzi. Concurrent murine virus infection resulted in increased pathogenicity of T. cruzi infection shown by profound thymic atrophy; loss of cortical thymocytes; depletion of Thy1.2+, CD4+, and CD8+ cells; enhancement of in situ labeling of nuclear DNA fragmentation; and eventually, death of the animals. Such lines of evidence show that the mechanism underlying this thymic atrophy is associated with apoptosis. These results also suggest that MHV-3 can account for the increased immunosuppression observed during experimental infection with the parasite.