The capacity of Fab and F(ab′)2 fragments to induce cytotoxicity of lymphocytes in vitro was studied. Target cells were chicken erythrocytes and effector cells purified human peripheral lymphocytes. Inducing antibodies were from rabbit immune serum against the target cells. Fab I, Fab II and F(ab′)2 fragments, obtained from the IgG fraction of such antiserum by digestion with papain or pepsin, respectively, had no inducing effect. In contrast, they inhibited cytotoxicity induction by undigested antibodies when the latter were added at slightly suboptimal concentrations. The results indicate that the intact Fc part of the anti-target cell antibodies is required for the cytotoxic reaction.