The capacity of rat peritoneal eosinophils to kill schistosomula of Schistosoma mansoni coated with antibody plus complement (C) (fresh immune rat serum) has been compared with that recorded when the parasites are coated with C alone (fresh normal rat serum) or antibody alone (heat-inactivated immune rat serum). Time course studies of adherence and killing, together with serum and cell dilution experiments, have revealed the superior efficiency of the system involving eosinophils, antibody, and C. Cell migration assays have shown that the combined factors generated when both the classical and alternative C pathways are activated at the parasite surface are more potent eosinophil chemoattractants than those generated from the alternative pathway alone. Moreover, faster and higher levels of eosinophil-mediated killing accompany the generation of such factors; 70 to 80% mortality being recorded within 3 hr as compared to 25% or less when the factors are absent. Experiments with fIRS chelated with EGTA indicate that more C3 molecules are probably bound to the parasite surface when C is activated via the classical rather than the alternative pathway, and that factors stimulating eosinophil migration generated from the classical pathway promote faster adherence and, as a consequence, higher levels of eosinophil-mediated killing. IgE does not seem to play an important role in eosinophil-mediated cytotoxicity in vitro, in the presence of fIRS, but the possible participation of the anaphylatoxins and ECF-A is discussed. It is suggested that the rapid and enhanced parasite killing effected by the combination of eosinophils, antibody, and C may be of paramount importance in the destruction of the schistosomula of a secondary infection in the immune host.