The involvement of IgG2a antibodies and mast cells in antibody-dependent eosinophil cytotoxicity suggested a possible interaction between mast cells and eosinophils for in vitro killing of Schistosoma mansoni schistosomula. Cell purification procedures showed that a minimum ratio of mast cells was required to obtain eosinophil cytotoxicity. The incubation of mast cells with heat-aggregated IgG2a immunoglobulins before addition to a mast cell-depleted eosinophil population induced a significant degree of inhibition of cytotoxicity. Similarly, the heat-aggregated IgG2a Fc fragment had a strong inhibitory effect whereas incubation of mast cells with Fab fragment failed to inhibit the cytotoxic effect. The Fc portion of IgG2a immunoglobulins therefore seemed to be involved in binding to the mast cell surface. Furthermore, it was demonstrated that soluble mediators released after mast cell activation either by compound 48/80, or by IgE, or IgG2a-dependent reaction had the same effect as intact mast cells. These observations suggest that the eosinophil-dependent cytotoxicity mechanism requires a signal provided by soluble mast cell mediators in addition to antibody.