SummaryThe infraction betweenEntamoeba histolyticatrophozoites and cells of the immune system was studiedin vitro. Both immune as well as non‐immune mononuclear cells (MNC) to some extent were capable of exerting a cytotoxic effect onE histolyticatrophozoites. Incorporation of immune serum directed against the trophozoites in the reaction mixture resulted in a marked increase in the killing capacity of MNC. Highest killing was observed (96·7 ± 1·04%) with MNC obtained from animals immunized with fraction‐1(F‐1) of the crude amoebic extract in association with anti‐F‐1 serum. This cytotoxic event was found to be independent of complement involvement and required very low antibody concentrations. This antibody‐dependent cellular cytotoxicity againstE. histolytica in vitrowas found to correlate well with the results of experiments reported earlier by us and others where a high degree of protection has been shown alter vaccination of animals with F‐1 followed by challenge with highly virulent strains ofE. histolytica.