Hybrid tumor cells were formed by the spontaneous and virus-induced fusion of EL-4 lymphoma cells with C3H fibroblasts. Some resultant hybrid cell lines specifically immunized C57BL/6 and (C57BL/6 × C3H)F1 mice against subsequent lethal EL-4 challenge. The immune response to the hybrid tumor cells was superior to the response to irradiated EL-4 cells. The possibility of hybrid tumor cells as a specific immunotherapeutic agent was discussed.