The relative merits of endogenous and exogenous oligodendrocyte progenitor cells (OPCs) for remyelination are compared in terms of their ability to repopulate OPC-depleted tissue and generate remyelinating oligodendrocytes. Exogenous neonatal OPCs can repopulate OPC-depleted tissue 5-10 times faster than endogenous cells and as a result are capable of more extensive remyelination. Both endogenous and exogenous cells will only repopulate normal tissue if there is extensive depletion of the local OPC population and both show reduced ability to generate remyelinating cells in the absence of acute inflammation. When endogenous OPCs are depleted by X-irradiation during cuprizone intoxication, where there is a combination of astrocytosis and acute demyelination, endogenous but not exogenous embryo-derived OPCs fail to repopulate the OPC-depleted cortex.