Human platelets in the presence of sera from humans with chronic Chagas' disease display cytotoxic activity against Trypanosoma cruzi (T. cruzi) trypomastigotes. Adsorption of IgE from those sera decrease the cytotoxic effect and IgG purified from the same sera revealed a cytotoxic action similar to the whole sera. Morphological studies suggest that chagasic serum promotes adhesion between parasites and platelets. On the basis of these results it is postulated that platelets may represent a defensive mechanism in South American trypanosomiasis by killing circulating forms of the parasite and that both IgG and IgE are relevant for that action.