A second histiocytic proliferative disorder, which resembled malignant histiocytosis of man, was identified in 13 Bernese mountain dogs. Malignant histiocytosis was clearly distinct from systemic histiocytosis, which was reported earlier in this breed. Eleven cases involved male dogs. Ten dogs occurred in the same family line as the dogs afflicted with systemic histiocytosis. Clinical or radiological evidence of pulmonary involvement was present in nine dogs. Neurological disturbances were present in five dogs. Anemia was observed in five dogs and was associated with prominent erythrophagocytosis in two instances. The clinical course was rapidly progressive. Necropsy examinations revealed that infiltrates were especially frequent in the lungs and hilar lymph nodes. Other lymph nodes, liver, spleen, and central nervous system were also frequently involved. Evidence for primary pulmonary involvement was present in seven dogs. The original diagnosis in seven cases was large cell anaplastic carcinoma of the lung by light microscopy only. The infiltrates were composed of large, pleomorphic, phagocytic mononuclear cells and multinucleated giant cells which also manifested marked cytological atypia and numerous, frequently bizarre, mitotic figures. Ultrastructural studies and the immunohistochemical demonstration of lysozyme and alpha 1-antitrypsin in the tumor cells in the majority of cases were consistent with a macrophage origin.