Precursor cells have the capacity to repopulate the demyelinated brain, but the molecular mechanisms that facilitate their recruitment are largely unknown. The low-affinity neurotrophin receptor, p75NTR, may be one of these regulators; however, its expression profile by oligodendroglia within the multiple sclerosis (MS) brain remains uncertain. We therefore assessed the expression profile of this receptor within 8 MS and 4 control brains. We found no evidence of expression of p75NTR by mature oligodendrocytes. Instead, we demonstrated the presence of p75NTR on a subgroup of NG2-positive oligodendroglial progenitors in a periventricular plaque in one MS sample. Notably, p75NTR-expressing cells were also detected within the subventricular zone (SVZ) of this brain, adjacent to the periventricular plaque. In animals with experimental demyelination we observed similar patterns of p75NTR expression, initially confined to precursor cells within the SVZ, followed at later stages in the disease course by its expression amongst a subset of oligodendroglial progenitors within the corpus callosum. These data suggest that a population of precursor cells within the SVZ can be induced to express p75NTR and to subsequently assume an oligodendroglial progenitor phenotype in response to demyelination in the adjacent white matter. © 2004 Wiley-Liss, Inc.