A 82-year-old male developed asymptomatic lymphadenopathy gradually increasing in submandibular region in 1985. Lymph nodes biopsied in 1987 showed massive proliferation of histiocytes with abundant clear cytoplasm, round nucleus, and occasional emperipolesis. Foci of marked plasmacytic infiltration and fibrosis were also seen in medullary and paracortical region. Immunohistochemically, most of the histiocytes were positive for S-100 protein, and a few were positive for lysozyme, α1-antitrypsin, and α1-antichymotrypsin. Ultrastructurally, the large histiocytic cells exhibited many lysosomes and marked interdigitation of cytoplasmic processes, but these cells lacked Birbeck granules. The patient had IgG antibodies to EBVCA and HTLV-I p 19. RA test and skin test with PPD were positive. No microorganism was detected by culture using biopsied lymph node and pharyngeal swab specimens. Histiocytic proliferation seen in this case resembled sinus histiocytosis with massive lymphadenopathy, though histogenesis was undetermined. A possible association of immunoresponses to EB virus and HTLV-I with unique differentiation and proliferation of histiocytes awaits further study.