Chronic GvHR was induced by inoculating parental lymphoid cells into F1 hybrid mouse. Combination of ATL and ATH, which were congenic recombinant strains differing only in H-2I and S region from each other, was chosen to induce class II-GvHR. Selective activation against partner's alloantigen of graft CD4+ T cells was the primary event of the GvHR and then led to concomitant activation of both graft and host cells. Immune dysregulation among these cells made the GvHR-mouse express various chronic diseases including immune complex glomerulonephritis, autoimmune-like lesions of the liver or the salivary gland, tumor-like proliferations of T cells and abnormal extramedullary hematopoiesis. Chronic GvHR was also induced by a preferential but not a selective activation of graft CD4+ T cells. A combination of DBA/2 and C57BL/6, which differ in whole MHC antigens, was an example. When D2 cells, but not B6 cells, were incoulated into the BDF1 mouse, predominant activation of CD4+ cells over CD8+ cells were observed. Contributing factors to this phenomenon were low responsiveness of graft CD8+ T cells to allogeneic class I MHC antigens and anti-parent activity of host CD8+ cells. Thus both graft and host cells participate either actively or passively in the reaction induced in the parent --> F1 experimental system of GvHR/D.