The role of Trypanosoma cruzi in the pathogenesis of myocarditis in the chronic phase of Chagas' disease is still controversial, with autoimmune mechanisms frequently being proposed. In the present work, we demonstrate that higher numbers of CD8+ T cells are correlated with the presence of parasite antigens, suggesting an important role for the parasite in the development of myocardial inflammation. Quantification of the mean numbers of CD8+ and CD4+ T cells per 400× microscopic field was performed in myocardial specimens from 33 chronic chagasic patients with heart failures (nine biopsies and 24 necropsies), using an immunoperoxidase technique. The cases were grouped according to a semiquantitative score of the relative amounts of T. cruzi antigens: group 1 = absent (14 cases); group 2 = scarce extracellular or intramacrophagic antigens (12 cases); group 3 = many extracellular or intramacrophagic antigens plus T. cruzi intramyocytic pseudocysts (seven cases). The mean numbers of CD8+ and CD4+ T cells in groups 1, 2, and 3 were 6.94 and 3.79, 13.89 and 6.24, and 17.91 and 5.97, respectively. The numbers of CD8+ T cells in groups 2 and 3 were significantly higher compared with group 1 (no T. cruzi antigens), but were not different from each other. Scarce, extramyocytic T. cruzi antigens were associated with an intense inflammatory infiltrate, suggesting that a delayed-type hypersensitivity immune mechanism is induced by the parasite; intact myocardiocytes containing parasites did not show an inflammatory reaction around them. A poor inflammatory response was frequently associated with many extramyocytic antigens and myocardial parasite pseudocysts, suggesting that active proliferation and dissemination of the parasites occur when the immunologic response is diminished. The number of CD4+ T cells did not vary significantly among the three groups. We conclude that the CD8+ T cell is the main cell type responsible for immune activation in chronic, human, chagasic myocarditis and is probably activated by the presence of T. cruzi antigens associated with internal myocytic host antigens. The absence of a significant member of CD4+ T cells in the presence of T. cruzi antigens suggests inhibition of CD4+ T cell activation or the lack of a class II major histocompatibility complex molecule presentation mechanism.