The antibody-dependent cell cytotoxicity (ADCC) to Trypanosoma cruzi blood forms (Btry) using non-adherent spleen cells is only mediated by sera from chronic chagasic patients or mice. Both display 'lytic antibodies' (LA), which are immunoglobulins directed against epitopes only present in living BTry, and 'conventional serology antibodies' (CSA), which are responsible for the positive diagnostic tests in Chagas disease. Sera from mice immunized with different T. cruzi antigens or from treated patients (displaying only CSA but not LA) are unable to mediate ADCC. These data confirm the central role played by LA in the host resistance against T. cruzi. Moreover, they probably explain why most immunizing agents used as vaccines in Chagas' disease and which elicit CSA but not LA, do not display significant protection against T. cruzi. We also demonstrate that trypsinization of BTry increases significantly the rate of parasite destruction by ADCC, suggesting that enzyme sensitive membrane components may help BTry to evade from this immune effector mechanism.