Mice neonatally infected with mouse mammary tumor virus (MMTV) are capable of antigen specific natural killer (NK) responses. As we have previously demonstrated, prior to 16 weeks, the C3H/HeJ female possesses natural killer cells capable of recognizing MMTV gp52 and MuLV gp71. After 16 weeks of age, a response to MMTV p28 is also present. These responses may be detected in vitro with the use of tumor target cells which express these antigens, and may be blocked in vitro by the addition of specific purified viral proteins and glycoproteins. Females of this strain bearing spontaneous mammary tumors of 15x15 mm or greater, demonstrate reactivity only against MuLv gp71. The spleens of these tumor-bearing females possess a cell capable of specifically suppressing NK responsiveness to antigens of MMTV, but not MuLv. We propose to investigate the significance, in this strain, of the arisal of an MMTV p28 response and its relationship to antigen expression of preneoplastic nodules; to define the precise timing of decline of immune responsiveness to MMTV gp52 and p28; and to investigate the nature of the antigen-specific suppressor cell described in this system. Based on findings in these studies, we will institute modes of therapy with purified antigens of MMTV. These treatments will be designed to alter pre-existing host levels of immune responsiveness to benefit the host in the prevention of tumors.