C3H mice, which are highly susceptible to infection with the Brazil strain of Trypanosoma cruzi, not only survive infection when maintained at elevated environmental temperature, but also experience reduced parasitemias, reduced tissue pathology, and enhanced immune responsiveness. The contribution of CD8 T cells to this phenomenon was investigated using the in vivo cell-depletion technique. The depletion of CD8 T lymphocytes with purified monoclonal antibody resulted in an abrogation of the protective effects of elevated environmental temperature during T. cruzi infection, as evidenced by high parasitemia levels and 100% mortality in monoclonal antibody–treated mice.