Previous studies from our laboratory have shown that rat lymphoid cells which were stimulated in an in vitro secondary immune response to a syngeneic virus-induced lymphoma developed the capacity to kill lymphoma cells and to inhibit tumor growth in vivo. The demonstration that the induction of cytotoxic T-lymphocytes (CTLs) involved the participation of tumor virus-specific helper T-cells responsive to antigens of murine leukemia virus (MuLV) represented a novel finding from these studies. In the present application we propose to continue studies in inbred mice to examine the nature of CTLs and CTL precursors which mediate inhibition of the growth of MuLV-induced syngeneic tumors and the availability of effector cell precursors in mice with progressively growing tumors. Additional experiments will explore the role of purified helper and suppressor T-cells and macrophages in regulating the induction of antitumor CTL responses in vitro. The role of each cell type will be defined first in normal and/or immune mice and then examined in mice with progressively growing tumors. The influence of purified viral antigens shed by tumors on the induction of effector cell responses will be further defined. These studies should clarify our understanding of host cellular immune mechanisms which regulate antitumor effector responses; they may provide a rational basis for inducing antitumor effector activity by otherwise unresponsive cells from mice with growing tumors.