The current findings in C57Bl/6 mice are consistent with previous reports of cuprizone treatment causing extensive demyelination of the corpus callosum in this mouse strain (13, 16, 24, 26) . To take further advantage of this model for examining mechanisms to promote remyelination from endogenous cells, we have further characterized the endogenous oligodendrocyte lineage population responses during the recovery period. We used C57Bl/6 mice for this part of our study to facilitate comparison with other studies, because differences in mouse strain can influence the response to cuprizone as well as overall cellular responses to CNS injury (13, 27) . After a transient episode of demyelination from 6 weeks of cuprizone ingestion, spontaneous remyelination is effective throughout the corpus callosum. In contrast, after a prolonged period of demyelination, from 12 weeks of continuous cuprizone, the remyelination remains limited and does not progress during a recovery interval that was examined out to 6 weeks. This limited remyelination corresponds with depletion of the OP pool ( [16] current study). However, the number of oligodendrocytes increases somewhat during the recovery period without a corresponding increase in remyelination of the corpus callosum. Taken together, these findings indicate that the depleted OP pool has a limited capacity to generate oligodendrocytes, and available OP cells may fail to fully differentiate into remyelinating oligodendrocytes in the environment of a chronic lesion. In lesions of some MS cases, immature oligodendrocyte progenitors and premyelinating oligodendrocytes may be present in relatively normal densities without efficiently remyelinating (9, 28) . Therefore, further studies will be important for better understanding regulation of the OP pool size and the transition of OP cells into premyelinating and then myelinating oligodendrocytes.