We recently reported that the cerebrospinal fluid (CSF) of patients affected by multiple sclerosis (MS) and the brain tissues of rats with experimental allergic encephalomyelitis (EAE) contain elevated levels of nerve growth factor (NGF). In the present study, we demonstrate that astrocytes and oligodendrocytes particularly localized in the white matter, including corpus callosum, overexpress NGFmRNA and produce NGF protein in the CNS of EAE affected rats. These findings indicate that the increased NGF found in the brain of EAE rats and most probably also in the CSF of patients affected by MS is produced by activated glial cells. It is hypothesized that the enhanced production of NGF by glial cells is necessary to compensate for the effect of axonal and/or neuronal cell body injury occurring in EAE. The possible functional significance of these findings in demyelinating diseases is discussed.