Two ligands for the epidermal growth factor receptor (EGF-R), EGF and transforming growth factor-α (TGFα), have recently been shown to influence the proliferation, differentiation or survival of diverse populations of fetal and neonatal neuronal and glial cells in culture. These findings suggest that EGF, TGFα, or another EGF-R ligand play a role in the regulation of similar cellular developmental events in vivo. In the present study, in situ hybridization with an ³⁵S-labeled cRNA probe was used to determine if mRNA for EGF-R is expressed in two principal germinal zones of the postnatal rat brain, the forebrain ventricular/subventricular zone and the cerebellar external granule layer. Cells labeled with the EGF-R cRNA were distributed throughout the subventricular zone, particularly in the dorsolateral aspect, from birth to adulthood, although the numbers of labeled cells as well as the density of hybridization diminished during development. In the developing cerebellum, virtually all cells in the external granule layer were densely labeled with the EGF-R cRNA, as were numerous perikarya throughout the molecular layer. EGF-R mRNA was also transiently expressed at lower levels by neurons of the internal granule layer and deep cerebellar nuclei. By adulthood, cerebellar expression of EGF-R mRNA was not detected. These results demonstrate prominent expression of EGF-R mRNA within germinal zones of the developing brain and indicate a role for EGF, TGFα, or another member of the EGF-related family in regulating the activities of neuronal and glial progenitor cells in vivo.