Macrophages in varying states of activation differ in their ability to perform antibody-dependent cellular cytotoxicity (ADCC). To define further the activation requirements for macrophages to perform cytolytic functions, we stimulated peptone-elicited peritoneal macrophages, which exhibit only a low level of ADCC, with a panel of cytokines and then assayed for the macrophages capacity to effect the rapid and slow forms of ADCC, to bind antibody-coated tumor cells, and to secrete H2O2 in response to immune complex or PMA. All four cytokine preparations, at optimal conditions, enhanced both forms of ADCC, but did not appreciably increase tumor cell binding. Three of the four cytokine preparations (Il-4, TNF and IFN-alpha/beta), however, increased the macrophages capacity to secrete H2O2 in response to either immune complex or PMA, IFN-gamma alone did not affect H2O2 secretion.