Remyelination occurs in demyelinated CNS regions in diseases such as multiple sclerosis. Identification of the cell type(s) responsible for this remyelination, however, has been elusive. Here, we examine one potential source of remyelinating oligodendrocytes-immature, cycling cells endogenous to adult white matter-and demonstrate that this population responds to demyelination by differentiating into myelinating oligodendrocytes. Dividing cells in subcortical white matter of adult rats were labeled by stereotactic injection of a replication-deficient lacZ-encoding retrovirus (BAG). Following a focal demyelination induced with lysolecithin, many of the BAG-labeled cells differentiated into myelinating oligodendrocytes engaging in repair of the lesion. Identification of endogenous cells capable of remyelination provides a target for the study of CNS repair processes in demyelinating diseases.