SummaryEosinophils and neutrophils are shown to be cytotoxic against two syngeneic mouse cell lines cells when these are coated with T. cruzi antigen and anti‐T. cruzi antibody. Activity is detected within 5 h of incubation. Highest levels of cytotoxicity are obtained at antibody dilutions of 1:100 and 1:1000, while antiserum at 1:10 is shown to be inhibitory. Eosinophils show significant activity at an effector to target ratio of 5:1. No cytotoxicity occurs in the absence of either antigen, antibody or effector cells. This phenomenon may be a model for the tissue destruction in acute T. cruzi infection, where the lysis of trypanosomes may lead to antigen coating of host cells, followed by antibody‐dependent granulocyte‐mediated cytotoxicity of the host