It was reported that Neurotropin (NSP) is a new immunostimulating agent which reverses the decrease of proliferation of irradiated spleen cells from mice caused by concanavalin A or specific antigen. The present study was undertaken to examine the possibility that NSP prevents graft-versus-host reaction (GVHR) through host-versus-graft reaction (HVGR) in mice. Allogeneic (C3H/He) spleen cells were performed intravenously into 900 R-irradiated recipient mice (BALB/c). Systemic GVHR was clearly prevented by NSP as well as by cyclophosphamide or prednisolone administered intraperitoneally into irradiated recipient mice. In recipient mice irradiated with 1000 R, a more remarkably systemic GVHR was induced as compared to recipients irradiated at 250 to 500 R. NSP suppressed the proliferation of donor cells at the induction phase of GVHR, whereas NSP did not inhibit both systemic and local GVHRs induced by cell transfer at the effector phase. A decrease in hematopoietic function following irradiation or dosing with immunosuppressive drugs was also reversed by NSP. However, NSP had no effect on increases in hematopoietic function mediated by syngeneic bone marrow transplantation into 900 R-irradiated mice. These results strongly suggest that the inhibition of allogeneic GVHR by NSP is responsible for the suppression of donor cell proliferation by adequately restoring immunologic function in irradiated recipient mice, namely HVGR.