A protocol of in vivo immune selection has been used to isolate a variant of the Moloney murine leukemia virus (MuLV)-induced tumor MBL-2. Characterization of the tumor variant indicated that selection resulted in the isolation of a cell which is incapable of producing infectious virus and no longer capable of synthesizing viral proteins. Although the failure to express viral Ag has rendered the variant tumor cells resistant to lysis by CTL specific for MuLV viral Ag, the variant tumor cells retained their susceptibility to lysis by CTL which appear to be directed against an MuLV-induced tumor-associated Ag. The data indicate that the expression of nonviral tumor-associated Ag by MBL-2 is not dependent upon continued viral gene expression.