Acute secondary disease was induced in (C57BL × CBA)F₁ mice by transplanting CBA bone marrow and spleen cells following lethal whole-body irradiation. The lesions of graft-versus-host (GvH) disease were scored quantitatively by counting of degenerated crypts in subcutaneous fetal gut implants that were free of bacteria. In conventional F₁ mice the damage in F₁ fetal gut was twice as great as in F₁ fetal gut implants carried by decontaminated chimeras. CBA fetal gut implants developed substantial damage when present in conventional chimeras, but not when present in decontaminated chimeras. These results could be explained by assuming the presence of cross-reacting antigens on intestinal bacteria and in the gut epithelial tissue. They also explained the profound protection against delayed GvH mortality provided by removal of the intestinal microflora.