SUMMARYThe local graft-versus-host (GVH) reaction reported by Ford et al. (4) has been applied to a murine model. In principle, the increase in number of nucleated cells contained in the popliteal lymph node of an Fi hybrid was determined after regional injection of immunocompetent parental strain spleen cells. This assay was used to test cell-mediated immune reactivity of spleen cells from casein-treated mice at various stages of amyloid induction. Concurrently, the test was applied to casein-treated donor mice presensitized with 2 consecutive allogeneic (second parental strain) skin grafts. The number of cells in the lymph nodes showed a linear relationship to logarithmically spaced numbers of cells injected. Marked depression of the GVH reaction was observed with spleen cells from nonsensitized donors treated with 10 and 20 daily injections of casein. In contrast, 10 injections of casein in the presensitized group did not affect the GVH reactivity of donor spleen cells. After 20 casein injections the same high degree of depression was encountered with spleen cells from both grafted and nongrafted groups of donor mice. In the presensitized and nonsensitized groups the same histological changes occurred under casein treatment, i.e., 10 casein injections gave rise to perifollicular pyroninophilia and 20 injections caused perifollicular amyloid deposits. The results are suggestive of cellular immune depression attributable to amyloid formation.