A syngeneic graft-versus-host disease (GVHD)-like syndrome has been shown to be inducible in some strains of mice after lethal irradiation, reconstitution with syngeneic bone marrow (BM), and treatment with a short course of CsA therapy. Since Thy1+ BM cells have been shown to regulate the development of other experimental autoimmune diseases, it was important to determine their role in the inducibility of syngeneic GVHD (SGVHD) in different strains of mice. Lethally irradiated mice were reconstituted with either syngeneic BM or T cell-depleted syngeneic BM, then treated with CsA or diluent. Removal of Thy1+ cells from BM before reconstitution of an inducible strain, C3H/HeN, exacerbated SGVHD when compared with animals given whole BM cells before CsA treatment. Furthermore, a noninducible strain, C57BL/6 mice, developed SGVHD when reconstituted with T cell-depleted syngeneic BM but not BM before CsA therapy. These results suggest that Thy1+ BM cells may regulate the development of SGVHD, and be of importance in controlling autoreactivity after bone marrow transplantation.