We isolated a neurotropic retrovirus, FrC6-V, from Friend leukemia virus complex after the adaptation of the original virus to newborn rat brain followed by the long-term infection of rat glioma cell line C6. When rats were infected with FrC6-V, the virus was isolated mainly from the brain and from the thymus of the infected animals regardless of the age of the animals at the time of inoculation. Neurological and neuropathological manifestations became apparent, however, only when the newborn rats were infected. The lesions in the brain were characterized by spongiform degeneration accompanied by the loss of neurons in the hypothalamus, cerebral cortex, and cerebellum. There was almost no inflammatory cell infiltration. In primary culture of brain, the astrocytes and the neuron specific enolase antigen-positive cells were infected with FrC6-V, but the viral antigen was not detected in neurofilament antigen-positive neurons. Furthermore, our virus inhibited the differentiation of embryonal carcinoma (EC) cell line P19 into neurons.