A number of ecotropic murine leukemia viruses (MLV) cause spongiform neurodegeneration without inflammatory infiltrates when infected into neonatal mice and/or rats.  One common feature of these viruses is that the primary determinant for induction of the neurodegenerative disease is the env gene that encodes the surface protein (SU) of the virus.  In the lesions of the brains of animals infected with these viruses, neuropil vacuolation is observed, whereas viral antigens are not or scarcely detected in neurons.  Viral antigens are mainly detected in endothelial cells in the brains of infected animals, and glial cells (astrocytes, oligodendrocytes, and microglia) also express viral antigens.  In some of the neuropathogenic viruses, including our isolate (A8), the studies of comparison of the distribution of the lesions and that of the viral antigen-positive cells indicate that microglial infection contributes to the induction of neurodegenerative disease.  Furthermore, in the brains of neonatal rats, many parechymal cells in addition to the vascular wall express the receptor protein for ecotropic MLV(CAT-1).  These observations suggest that the infection of retrovirus receptor-bearing glial cells, especially microglia, plays an important role in the induction of spongiform neurodgeneration.