Three hybrid cell lines were derived from the fusion of BALB/c mouse NS-1 myeloma cells and human acute lymphocytic leukemia cells. Hybrid clones contained almost all of the mouse chromosomes and a few human chromosomes, and induced tumors in BALB/c and BALB/c nu/nu mice when inoculated subcutaneously. However, the tumors of BALB/c mice subsided spontaneously within one month. The mice which survived the inoculation of 5 approximately 10 X 10(6) hybrid cells were able to reject a subsequent challenge with 5 X 10(6) NS-1 cells. Spleen cells or lymph node cells from immune mice were injected into BALB/c mice. These mice lived longer than the mice which received normal spleen cells or normal lymph node cells, when challenged with 5 X 10(6) NS-1 cells. These results suggest that a rearrangement of tumor-specific antigens on human/mouse hybrid cells can induce immunogenicity.