Acute graft-versus-host disease (a-GVHD) is one of the major complications in the allogeneic bone marrow transplantation (BMT) treatment of lympho-hemopoietic malignancies. The process is initiated primarily by immunologically competent cytotoxic T cells (CTLs) that express anti-host specificities, but the host lymphoid compartment in which the precursor CTLs are stimulated has been unclear. In the January 13 advanced online Nature Immunology, Masako Murai and colleagues at The University of Tokyo, Japan, show that Peyer's patches (PPs) are the essential site in the initiation of acute and lethal graft-versus-host reaction (Nature Immunology, doi:10.1038/ni879, January 13, 2003).