The goal of this study was to determine whether deposition of complement C3 breakdown products on the surface of HIV-infected target cells could augment the levels of antibody-dependent cellular cytotoxicity (ADCC) mediated by peripheral blood mononuclear cells (PBMC). Although C3 was deposited on the surface of infected cells in the presence of anti-HIV antiboby from infected persons, no increase in the levels f ADCC mediated by freshly isolated PBMC was seen with either infected H9 or CEM-NK r traget cells. However, a significant increase in ADCC was observed due to deposition of C3 on target cells with Il-2-stimulated effector cells. these results show that C3 deposition on target cells can increase ADCC cytotoxicity under certain conditions. Complement maythus contribute to destruction of HIV-infected cells through this mechanismin vivo, although these experiments suggest that specific antibody is the major targeting molecule for ADCC.