Cyclosporin A (Cy A; 15 mg/kg s.c.) allows allogeneic histoincompatible skin graft survival in 10 of 10 rabbits as long as the drug is given. The same dose of Cy A does not affect acute graft-versus-host disease (GVHD) and increase survival of rabbits after allogeneic bone marrow transplantation between the same two strains, when two groups of 15 animals are tested. Median survival of 14 engrafted animals without Cy A was 23 days, of 12 engrafted animals with Cy A 22 days (not significant). Cryopreservation of bone marrow delays the onset of GVHD and increases survival of engrafted animals. Median survival of 5 engrafted animals without Cy A was 33 days, of 14 engrafted animals with Cy A 35 days. Our hypothesis is that one part of early GVHD as well as of early graft rejection is mediated by a subclass of cells which is resistant to Cy A. This hypothesis is supported by the finding that most transplanted skins show a self-limited period of infiltration and induration. Skin grafts survive this period of infiltration. If the same potentially self-limited process occurs in the liver or the intestine during acute GVHD, animals die. this hypothesis could explain why Cy A allows skin graft survival but does not affect acute GVHD.