Hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation can occasionally cause graft failure. We describe a female patient with B-cell non-Hodgkin's lymphoma (NHL) with graft failure due to HPS 12 days after autologous peripheral blood stem cell transplantation (PBSCT). Autologous PBSCT was carried out during unconfirmed/uncertain complete remission according to the Cotswolds classification after 6 cycles of biweekly (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and 3 courses of salvage chemotherapy including etoposide. The patient developed a high fever on day 2 post-PBSCT. Her white blood cell count rose to 0.9 x 10(9)/L on day 10 post-PBSCT, but then began to decrease. A bone marrow aspirate on day 12 post-PBSCT revealed an increase in the number of benign histiocytes with hemophagocytosis, and the patient was diagnosed with HPS. Although high-dose methylprednisolone therapy was continued, her white blood cell count further decreased to 0.3 x 10(9)/L, and the patient died of multiple organ failure on day 29 post-PBSCT. A computed tomography scan did not identify recurrent NHL, and necropsy specimens from the bone marrow, liver, and kidney revealed no neoplastic infiltration. Bone marrow necropsy showed marked hypocellularity with active histiocytic hemophagocytosis. HPS may have been induced by infection with methicillin-resistant Staphylococcus aureus rather than by lymphoma-associated HPS.