The LP-BM5 retrovirus, a complex containing ecotropic helper, recombinant MCF, and defective retroviruses, causes an immunodeficiency-termed mouse AIDS (MAIDS). Many disease features of MAIDS resemble those of AIDS, including terminal B cell lymphomas. Previously we generated from MAIDS-susceptible C57BL/6 mice cytolytic T lymphocytes (CTL) specific for MAIDS-associated B cell lymphomas. Data of the present study (1) exclude MCF and establish a role for defective virus in generating C57BL/6 CTL to MAIDS-associated tumors by experiments involving in vitro stimulation with cells from LP-BM5, ecotropic, or ecotropic-rescued defective virus-infected mice and (2) confirm that such CTL are specific for tumors of MAIDS origin. Several approaches testing for direct involvement of defective virus or its gag-encoded polyprotein, however, did not provide evidence that MAIDS tumor-specific CTL were directed to structural virion proteins, suggesting the possibility that such CTL are specific for nonvirion antigens whose expression depends on the action of the defective genome in the MAIDS disease process.