Normal human polymorphonuclear leukocytes (PMN) are cytotoxic to T. cruzi epimastigotes sensitized with specific antiserum (T. cruzi + Ab). The damage follows an early phagocytic event, suggesting the intracellular destruction of the parasites. We have studied the characteristics of the killing using metabolic inhibitors of the effector cells. Oxygen consumption by PMN with unsensitized parasites was similar to the uptake by resting cells, but increased two- to fourfold when T. cruzi + Ab was used. This increase in O2 consumption, associated with phagocytosis of T. cruzi + Ab was not sensitive to 2 mM cyanide nor 100 microM azide. Addition of T. cruzi + Ab to human PMN also stimulated H2O2 production. When PMN were incubated with phenylbutazone, cyanide or azide, an inhibition of cytotoxicity against sensitized T. cruzi was observed. Under the same experimental conditions phagocytosis was unaffected. These results indicate that active oxygen reduction products and myeloperoxidase are involved in the destruction of sensitized, T. cruzi epimastigotes by normal PMN.