The adult mouse forebrain, which exhibits substantial ongoing cell genesis, contains self-renewing multipotent neural stem cells that respond to epidermal growth factor (EGF), but the adult spinal cord, which exhibits limited cell genesis, does not. Spinal cord development is a process characterized by defined periods of cell histogenesis. Thus, in the present study we asked whether EGF-responsive neural stem cells are present within the spinal cord during development. At embryonic day (E) 11, subsequent to the onset of neurogenesis, only fibroblast growth factor (FGF) receptors and FGF-2 (requiring heparan sulphate)-responsive stem cells are present in the spinal cord. Between E12 and 14, at the peak of spinal cord neurogenesis and the onset of gliogenesis, EGF receptors appear along with clonally derived highly expandable EGF-responsive neural stem cells. Following the cessation of cell histogenesis, the adult spinal cord is largely devoid of both EGF receptors and EGF-responsive stem cells. On the other hand, the FGF receptor1c subtype and multipotent FGF-2-responsive neural stem cells are present in early development and in the adult. The order of appearance of spinal cord neural stem cells and in vitro lineage analysis suggests that a more primitive FGF-2-responsive stem cell produces the EGF-responsive stem cell. These findings suggest that EGF-responsive neural stem cells appear transiently in the spinal cord, during the peak period of cell histogenesis, but are no longer present in the relatively quiescent adult structure.