Graft-versus-host disease (GVHD) after liver transplantation is uncommon but is a serious complication that can be fatal. Hemophagocytic syndrome (HPS), which is caused by activation of autologous T lymphocytes, is also a serious complication that can occur after liver transplantation. Because these complications share the clinical triad of skin rash, marrow failure, and diarrhea, differential diagnosis is difficult. We describe a case of severe GVHD resembling HPS in clinical features that occurred after living-related liver transplantation. The patient who had undergone the transplantation had high fever, pancytopenia, and skin rash 3 wk after the operation. Examination of a bone-marrow biopsy sample revealed the presence of abundant monocytes with phagocytosis, suggesting either GVHD or HPS. Donor human leukocyte antigens were detected in the peripheral blood of the patient by polymerase chain reaction, but this finding is not specific for GVHD. A definitive diagnosis was made by demonstration of remarkable anti-self response and undetectable anti-donor response in a mixed lymphocyte reaction assay using carboxyfluorescein diacetate succinimidyl ester.