Mice infected with murine leukemia virus (MuLV) as neonates or carrying MuLV secondary to milk transmission (carriers) also develop complex autoaggressive responses. By a sensitive in vitro microcytotoxicity assay, neoplastic or pre-neoplastic thymocytes from carrier mice were found to react vigorously against normal uninfected syngeneic embryonic fibroblasts, whereas they reacted much less vigorously with similarly prepared but MuLV-infected fibroblasts. Thymocytes from uninfected animals did not react with infected or uninfected fibroblasts. Peripheral lymphocytes from young carriers reacted against MuLV-infected fibroblasts, but not against uninfected fibroblasts, a pattern indistinguishable from deliberately-immunized mice. We shall attempt to clarify the roles of immune responsiveness, both normal and autoaggressive, in the pathogenesis of virus-induced murine lymphomas. Utilizing the MuLV-M carrier model, we shall: 1. Further characterize the autoaggressive response of carrier thymocytes including identification of the cell type (i.e., "T-cell," "B-cell" or adherent cell; sensitivity to cortisone), determination of whether the effector cells are infected with MuLV-M, and exploration of the mechanism(s) leading to MuLV-M induced autoreactivity. 2. Attempt to correlate in vitro autoreactivity by carrier thymocytes with in vivo autoreactivity. 3. Further define the host immune responses (both cellular and humoral) against MuLV-M in virus carrier mice and evaluate the interrelationships between antiviral and anti-"self" reactivity at different stages during the preleukemic period.