The adult brain contains a large population of glial cells with the properties of oligodendrocyte precursor cells (OPCs). The functions of this newly recognized class of glial cells in normal animals are unknown. Here, we analyzed the reactions of OPCs to a transient demyelination of the rat brainstem induced by the injection of ethidium bromide (EB) into the fourth ventricle. Within 22 h after EB injection, there is a 21% decrease in the number of OPCs within affected fiber tracts such as the spinal tract of the trigeminal nerve, most likely reflecting the toxic actions of EB. The surviving OPCs had enlarged cell bodies with fewer long processes and many membrane blebs. By 2 days after EB injection, these reactive OPCs had incorporated BrdU and increased in number. The increase in OPC cell number reached a maximum between 6-10 days after EB injection, at which time demyelination was complete. Myelin-specific marker antigens reappeared beginning at 12 days postinjection and the remyelination continued for up to 40 days. During remyelination, OPCs displayed a normal stellate morphology with an increased number of thin processes, many of which were closely associated with neurofilament-positive axonal profiles. The transient increase in the number of reactive OPCs within the demyelinated tissue and subsequent decrease in OPC number during remyelination demonstrates that the endogenous oligodendrocyte precursor population responds rapidly to the pathophysiological state of the brain. Demyelination generates a sufficient number of OPCs to participate in the repair of the demyelinated lesions.