A 48 year-old male was admitted with cough, abnormal shadow on chest X-ray film and continuous fever which showed no response to antibiotics.On admission, peripheral blood examination revealed slight anemia (Hb 10.3g/dl), slight increase of percentage of monocytes (16%) without leukocytosis and increase of ESR. Other laboratory data revealed slight hyperbilirubinemia and elevation of serum transaminase. Concerning tumor marker, marked elevation of ferritin and IAP were detected.Chest X-ray film on admission, showed a reticulo-nodular pattern of bilateral lower lung fields, suggesting interstitial pulmonary disease. Fever did not respond to antibiotics, so 60mg/day prednisolone was administered. Shortly after, fever decreased but only transiently.We performed several diagnostic technique, TBLB, bone marrow biopsy, and lymph node biopsy. Anemia and jaundice increased gradually, and the general condition worsened. Histological examination of the biopsy specimen revealed large mononuclear atypical cell proliferation. This was recognized as atypical histiocytic proliferation by electromicroscopical, immunohistochemical, and chromosomal analysis.Finally, the patient was treated with ACNU (100mg). Then the general condition of the patient rapidly improved. At 15 months from onset, the general condition of the patient continues to be good.Malignant histiocytosis is characterized by systemic, progressive, fatal disease. Pulmonary involvement is not a rare complication of the disease. Previous reports described a 30-40% incidence of pulmonary involvement. We reviewed the Japanese cases reported in the last 10 years (1975-1985), there were 28 reported cases, 11 of which had pulmonary involvement confirmed by autopsy.In this case, we performed chromosomal analysis of the bone marrow biopsy specimen. An abnormal clone was identified (chromosome number: 75, mainly near tetraploid karyotype, and a couple of marker chromosomes).For the histopathological study of this case, we used immunohistochemical techniques employing lysozyme, alpha-1-antitrypsin, S-100 protein. Specimens of both the pulmonary lesion and bone marrow were positive for lysozyme and alpha-1-antitrypsin but negative for S-100. There are many different ideas about the reactivity of immunohistochemical markers. Some investigators suggest that malignant histiocytosis is derived from a “monocyte-histiocyte lineage”, white other claim that it is derived from a “T-zone histiocyte lineage” Therefore there is a difference between the two concerning the reactivity of immunohistochemical staining. Up to the present, there is no commonly accepted assessment of the reactivity of immunohistochemical markers.This case was treated with ACNU only, which was very effective for this patient. In the Japanese literature there is another report of malignant histiocytosis effectively treated with ACNU. These results show that ACNU can be effective in the treatment of malignant histiocytosis.