Fetal ependyma is an active secretory structure for the programming of developmental events, including the arrest of neuronogenesis, the guidance of axonal growth cones, motor neuron differentiation, and probably also the maintenance and transformation of radial glial cells that guide migratory neuroblasts. The floor plate, induced by the notochord, is the first part of the neuroepithelium to differentiate. It establishes polarity and growth gradients of the neural tube and has immunohistochemical features that differ from all other regions of the ependyma. The dorsal and ventral median septa, formed by floor and roof plate ependymal processes, prevent aberrant decussations of developing long tracts, but permit the passage of commissural axons. Fetal ependyma synthesizes several intermediate filament proteins absent from mature ependymal cells, although some are also expressed in undifferentiated neuroepithelial cells. Fetal ependyma also produces diffusible molecules, such as neural cell adhesion molecule, proteoglycans, nerve growth factor, and S-100 protein, all in specific temporal and spatial distributions. Maturation of the ependyma is not complete until the postnatal period. An abnormal fetal ependyma may play a primary role in the pathogenesis of some cerebral malformations, such as lissencephaly/pachygyria and holoprosencephaly.