Spleen cells from syngeneic tumor-bearing mice were examined for direct cell-mediated cytotoxicity (DCMC) and lectin-dependent cell-mediated cytotoxicity (LDCC). In the DCMC assay specific cytotoxicity against the homologous tumor cell was assessed. In the LDCC assay cytotoxicity was nonspecifically assessed against EL-4 cells in the presence of concanavalin A or phytohemagglutinin. Most tumor lines tested (19/22) produced no cytotoxic reactivity in either the DCMC or LDCC assays. In the case of the remaining tumor lines (EL-4, BW5147-3, and P815 Y-3), significant LDCC, but not DCMC, was detected, which indicated that although cytotoxic effector cells had been activated, the reactivity was not directed toward the homologous tumor cell or could not be expressed in the DCMC assay. The EL-4 and BW5147-3 cell lines proved to be sporadic in terms of their ability to induce LDCC, whereas the P815 Y-3 cell line produced consistent LDCC. Reactivity induced by P815 Y-3 cells appeared to be due to the constitutive production and release of a soluble component which could activate cytotoxic T-cells in vivo.