Adult-onset demyelinating disorders of the central nervous system represent the most common neurological abnormalities in young adults. Nevertheless, our understanding of disease pathogenesis and recovery in demyelinating disorders remains incomplete. To facilitate investigation into these processes, we have developed a new mouse model system that allows for the induction of dipththeria toxin A subunit expression in adult oligodendrocytes, resulting in widespread oligodendrocyte loss and demyelination of the central nervous system. These mice develop severe ataxia and tremor that correlates with impaired axonal conduction in the spinal cord. Strikingly, these animals fully recover from their motor and physiological defects and display extensive oligodendrocyte replenishment and widespread remyelination. This model system demonstrates the robust reparative potential of myelin in the central nervous system and provides a promising model for the quantitative assessment of therapeutic interventions that promote remyelination.