A syndrome akin to graft-versus-host disease in the recipient of syngeneic stem cells is hitherto described as being milder, self-limiting and confined to the skin. It is enhanced by prior cyclosporin A therapy. We describe here a recipient of a syngeneic marrow transplant who did not receive priming with cyclosporin A and yet developed severe and progressive graft-versus-host disease which necessitated and responded to high-dose immunosuppressive therapy. We believe that this is because the conditioning regimen in stem cell transplant acts to reset the immune system enabling it to recognise 'self' antigens. Bone Marrow Transplantation (2000) 25, 205-207.