Hemophagocytic syndrome is a proliferative disorder of an activated monocyte-macrophage system and is characterized by fever, hepato-splenomegaly and pancytopenia. The serum level of interferon-gamma in the syndrome is increased but its origin is unknown. Here we describe a case of NK cell leukemia with hemophagocytic syndrome with elevated serum level of interferon-gamma. The levels of various cytokines were monitored during the course and statistic analysis was performed. To identify the clonal component, the NK cell fraction was sorted from the mononuclear layer and was subjected to Southern blot hybridization with a probe for EB virus tandem repeats. The fraction was also stimulated with interleukin-2 and the level of interferon-gamma in the conditioned medium was measured. Levels of M-CSF and interferon-gamma were significantly correlated with the degree of clinical manifestations and laboratory data. Southern blot hybridization revealed monoclonality of an NK cell fraction. The fraction also released interferon-gamma. Since macrophage can be activated through cytokines, the hemophagocytosis might have been triggered by factor (s) released from the abnormal NK cell clone at least in this case.