We induced active demyelination in mice by adding 0.2% cuprizone to the diet so that return to normal chow would allow analysis of spontaneous remyelination without ongoing disease pathogenesis. Cuprizone reproducibly demyelinates the corpus callosum of mice (13) . Spontaneous remyelination is greatly reduced after chronic cuprizone demyelination in contrast to acute demyelination (14 Y 16) . Importantly, after chronic cuprizone demyelination, axons remain viable and can be remyelinated by transplanted OP cells (16) . In this chronic demyelination model, the current study demonstrates dramatically improved remyelination by endogenous cells in mice with genetic deletion of FGF2 as compared with wild-type mice. Thus, FGF2 expression in chronic lesions may limit remyelination and attenuation of FGF2 may generate a sufficiently permissive environment for spontaneous remyelination by endogenous cells.