Lethally irradiated mice treated with heterologous rat bone marrow (950-r RBM chimeras) were either splenectomized or sacrificed for spleens at various intervals after treatment. Injection of these chimera spleen cells into lethally irradiated recipients resulted in the production of antibody to rat RBC antigen detectable in the serum 7 days after transfer. Under the appropriate experimental conditions this antibody-forming activity was attributable to the chimera spleen, and not the irradiated recipient, which served primarily as an in vivo tissue culture for the cells. In contrast, injection of the chimera spleen cells into midlethally (800 r) irradiated rats did not result in agglutinin formation to mouse RBC antigen when the serum of the recipients was tested at intervals from 3 to 10 days after transfer. These data support the thesis that in the heterologous chimeras there exists an immunologic reaction of the irradiated host against antigens of the foreign graft, and this in vivo antigen-antibody reaction is the underlying mechanism of the secondary disease syndrome observed in these animals. Evidence for graft reactivity against the host was not apparent in this experimental design.

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