ABSTRACT. Canine necrotizing meningoencephalitis (NME) and granulomatous meningoencephalomyelitis (GME) were compared pathologically. Gross observation exhibited lateral ventricular dilation and discoloration, malacia and/or cavitation of the cerebrum in NME. On the contrary, gross changes were milder in GME, except for occasional visible granulomatous mass formation. Histopathologically, the lesions of NME were distributed predominantly in the cerebral cortex and various degrees of inflammatory and necrotic changes were observed according to clinical stages. Besides, microscopic lesions of GME were mainly distributed in the white matter of the c erebrum, cerebellum and brainstem, which are characterized by perivascular cuffing, multiple granulomas and leptomeningeal infiltrates. Although macrophages and lymphocytes were predominant in the inflammatory lesions of both disorders, macrophages in GME transformed into epithelioid cells and exhibited more massive infiltration. Although lectin RCA-1-reactive cells were numerous in both disorders, lysozyme immunoreactive cells in NME were fewer than that in GME. Parenchymal infiltration of MAC387-positive cells was common in GME and limited in NME. The number of CD3-positive lymphocytes in the GME lesions tended to be greater than in NME, though the difference was not statistically significant. Morphological and immunohistochemical differences of the lesions, in particular, the characteristics of infiltrative macrophages may reflect these different pathogeneses of the two disorders. KEY WORDS: canine, granulomatous meningoencephalomyelitis, macrophage, necrotizing meningoencephalitis.J. Vet. Med. Sci. 65(11): 1233-1239, 2003 Canine necrotizing meningoencephalitis (NME) is a unique inflammatory disorder in small-sized breed dogs, especially in Pug dogs. The disease is histopathologically characterized by inflammatory changes consisting of lymphocytic, plasmacytic and histiocytic infiltrations and apparent parenchymal necrosis located mainly in the cerebral cortex [9,15,23]. The common clinical features are forebrain signs such as partial or generalized seizure, decreased consciousness, abnormal behavior, circling and ataxia [9,23]. The cause of NME is still unknown. However, our previous report showed that a certain autoantibody against a canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum, which may suggest an autoimmune pathology in NME [25].The pathological features of NME are often compared with granulomatous meningoencephalomyelitis (GME) that is another inflammatory disease of unknown cause [5,8,23]. Although there are some differences such as breed predilection, the distribution of lesions and the presence or absence of necrotic foci, GME and NME show similar histological changes, i.e., meningitis and perivascular cuffing composed of mononuclear cells including lymphocytes and monocyte/histiocyte-lineages [5,8,23]. Kipar et al. [14] revealed lesions in GME are predominantly composed of CD3 antigen-positive T lymphocytes and a heterogeneo...