A number of studies have demonstrated that a moderate immune reaction may augment the response to chemotherapy. Two approaches are examined in the current report: (a) chemoimmunotherapy with viable L1210 cells that were antigenically altered by treatment with DTIC (L1210/DTCI), and (b) chemotherapy plus treatment with lymphocytes from mice immunized against L1210/DTCI. Treatment of the parental leukemias L1210 Ha and L1210 Cr with BCNU or cyclophosphamide in combination with viable antigenically altered tumor cells and with lymphocytes immunized against the antigenically altered tumor cells resulted in marked therapeutic responses. The observations suggest that these combined therapeutic modalities are worthy of investigation employing human tumors.