We have demonstrated, with optical and transmission electron microscopy, that Trypanosoma cruzi trypomastigotes infect and multiply inside T lymphocytes. The infection rate we have observed in T cells was similar to that seen in the case of macrophage or polymorphonuclear cell infection. Flow cytofluorometric analysis of T lymphocytes purified from mice in the acute phase of the disease, revealed the presence of parasite-derived antigens on their surface. These antigens appear to be specific to T. cruzi and they could be the result of intracellular parasite antigens as well as adsorption of T. cruzi antigens on the surface of noninfected T cells. Antibodies recognizing these surface antigens were present in both T. cruzi-infected mouse and human sera. They were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of nonimmune mononuclear cells both in autologous and in heterologous combinations. Consequently, we provided evidence suggesting that T lymphocytes could be destroyed during the acute phase of Chagas' disease either by cell infection or by an ADCC mechanism against cells bearing parasite antigens on their surface. Thus, the ability of trypomastigotes to invade T cells may play a crucial role in the immunopathogenesis characteristic of Chagas' disease.