Serum cytokines, lymphocyte subsets of peripheral blood and natural killer cell activity were serially assayed in a 3-year-old girl with hemophagocytic syndrome. Laboratory findings showed pancytopenia, increased levels of transaminases and hyperferritinemia and proliferation of histiocytes in bone marrow and pleural effusion. The administration of prednisolone resulted in a temporary improvement followed by a further exacerbation. The patient died in spite of the treatment with VP-16 and THP-adriamycin. Serum interferon-gamma (IFN-gamma) markedly increased in active phases. TNF-alpha, IL-1 beta and GM-CSF concentrations were normal or slightly elevated. The CD4/8 ratio of peripheral lymphocytes and natural killer cell activity also fluctuated according to clinical stage. These results suggested that IFN-gamma was the most important cytokine to activate histiocytes in this case.