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The article discusses the diagnosis of patient with Hemophagocytic lymphohistiocytosis (HLH) syndrome, an uncommon syndrome described after exposure to various infectious agents. HLH has two forms--the primary or familial form, and a secondary or reactive form. The clinical syndromes of HLH are prolonged fever, hepatosplenomegaly, and cytopenia, proceeded by an upper respiratory or GI infection. Patients should be carefully followed up for remission, reactivation, or development of lymphoma.