AbstractSJL/J mice are a genetically low‐NK strain, and their cytotoxic activity cannot be augmented with conventional NK inducers. In contrast, effector cells taken from the lymphoid tissues of SJL mice bearing a syngeneic B cell lymphoma (RCS) show variable, but significant levels of cytotoxic activity against NK‐susceptible targets, such as YAC‐1. Previous results suggested that the RCS cells themselves contributed to this cytotoxicity. However, results presented here indicate that most, if not all of the activity present within the lymphoid tissues of RCS‐bearing mice is mediated by RCS‐activated, host NK cells. These results were confirmed by in vitro studies, which demonstrate that both gamma irradiated (γ‐) RCS cells and γ‐allogeneic spleen cells induce cytotoxic activity in SJL spleen cells against YAC targets. However, the cytotoxicity induced by γ‐allogeneic cells is mediated largely by lymphokine‐activated killer (LAK) cells, since these effectors also lyse NK‐resistant target cells, such as L1210. In contrast, the cytotoxic effector cells that are induced by syngeneic γ‐RCS cells cause lysis of YAC targets, but not L1210 target cells. These data indicate that the syngeneic B cell lymphomas of SJL mice are a unique stimulus for host NK cells in this strain. Since activated NK cells produce a variety of lymphokines, RCS stimulation of host NK cells in SJL mice may provide some of the growth‐promoting lymphokines that are known to be necessary for progressive growth of these lymphoma cells.