Our overall goal in these studies is to investigate the mechanisms involved in the development of MMTV-specific natural killer cell reactivity and to determine what factors control the decline of this reactivity following spontaneous tumor development in the host neonatally infected with MMTV. We have investigated both nude (athymic) and conventional mice and have found both to possess substantial levels of antigen-specific NK activity to MMTV gp52 and p28. This reactivity declines sharply following spontaneous tumor production. We wish to determine the lineage of the NK cells both in terms of antigen commitment and end point differentiation, and to determine whether there are previously undetected subpopulations of NK cells which recognize "transformation" antigens in addition to viral antigens.