In order to develop a more effective method of immunotherapy we have transfected mouse interleukin‐2 (IL2) or mouse interleukin‐4 (IL4) cDNA into a spontaneous non‐immunogenic murine lung cancer, Lewis lung carcinoma (LLC). IL2 cDNA transfection more strongly decreases tumorigenicity of LLC than IL4 cDNA transfection. Recombinant‐human‐IL2 treatment of mice that were transplanted with untransfected LLC could not prolong their survival. In contrast, vaccination with IL2‐cDNA‐transfected LLC (LLC‐IL2) and LLC‐ILZ mixed with IL4‐cDNA‐transfected LLC (LLC‐114) could significantly suppress tumor growth of LLC in a tumor‐specific manner. The vaccination with LLC‐IL2 mixed with the same number of LLC‐IL4 cells was more suppressive to the growth of LLC than that with LLC‐ILZ cells alone, while LLC‐IL4 vaccination alone was ineffective. Nude, severe‐combined‐immune‐deficient (SCID) and beige mice were unable to reject LLC‐IL2 cells. However, immunodeficient mice responded to LLC‐IL2, but not to LLC, since their survival times after transplantation with LLC‐IL2 cells were significantly longer than the survival time of normal or immunodeficient mice transplanted with untransfected LLC cells. We conclude that vaccination with IL2‐producing tumors and, with more pronounced effect, in combination with IL4‐producing tumors, is able to induce an immune response to this normally non‐immunogenic tumor. Tumor rejection appears to be achieved by the combined activity of CTL and NK cells. This strategy has potential for new immunotherapeutic interventions in cancer patients.