Lymphadenitis with massive hemophagocytic sinus histiocytosis has been reported in patients with scleroma and in cervical lymph nodes of children without any known etiologic condition. Using electron microscopy, we conducted the present study on submandibular enlarged lymph nodes from a 6-year-old girl with this condition. Examination revealed marked dilatation of the sinusoids due to extensive sinus histiocytic proliferation. The most conspicuous feature is phagocytosis of blood cells, predominantly of lymphocytes, by histiocytes. Engulfment of granulocytes, plasma cells and plasma cell precursors is less significant. Erythrophagocytosis is rare. Initially, the phagocytosed cells appear well preserved. Eventually, however, the engulfed cells are completely digested. Hemophagocytosis is less pronounced in histiocytes of the pulp. The blood vessels contain an abundance of monocytes. It is concluded that histiocytes of the pulp and of the sinuses are derived from emigrated blood monocytes. Two main kinds of sinus histiocytes are distinguishable: One type exhibits only faintly staining cytoplasm. The second type shows striking eosinophilia of the cytoplasm having a tendency to giant cell transformation with one or multiple nuclei. Type 1 sinus histiocyte shows prominent hemophagocytosis. Phagocytic activity is less pronounced in type 2 sinus histiocyte which, ultrastructurally, exhibits long slender cytoplasmic processes like those described in epithelioid cells. The inflammatory nature of this condition is indicated by the profuse infiltration of the pulp by plasma cells which are thought to be connected with the production of humoral antibodies. This leads one to suspect that antibody-mediated opsonization of the ingested blood cells is responsible for the hemophagocytic process. However, it cannot be excluded that hemophagocytosis is merely the result of a nonspecific stimulation of the sinus macrophages by infectious organisms. The failure to demonstrate microorganisms is not incompatible, of course, with an infectious etiology. The organisms may be only briefly present at the time of initial infection supplying the stimulus for the primary process resulting in this peculiar inflammatory reaction.