The capacity of multipotential progenitor cells of the adult mammalian forebrain to generate myelin-forming oligodendrocytes was tested by grafting fragments of different regions of the subventricular zone (SVZ) of the lateral ventricle and the striatum of 6-month-old wild-type mice into the brain of neonate shiverer and wild-type mice. Without growth factor treatment, only few cells of the rostral SVZ survived and formed myelin after engraftment. Treating donors prior to transplantation with a single intraperitoneal injection of epidermal growth factor, basic fibroblast growth factor 2 (FGF-2), and platelet-derived growth factor AB (PDGF(AB)) vigorously promoted the survival, migration, and differentiation of the grafted SVZ cells into myelin-forming oligodendrocytes. In situ, both growth factors expanded the constitutively proliferative PSA-NCAM+ population and favored their differentiation toward the neuronal and oligodendroglial cell fate. The adult central nervous system thus harbors a focal reservoir of FGF-2 and PDGF(AB)-responsive cells which are able to generate substantial amounts of myelin-forming oligodendrocytes in vivo, opening a new prospective area for therapy in demyelinating diseases.