Epidermal growth factor receptor (EGFR), a 170-kDa transmembrane glycoprotein, appears to mediate epidermal growth factor (EGF) activity. Transforming growth factor-alpha and EGF produce their biological effects in numerous systems by stimulating the EGFR. In the present study, we examine the postnatal development of EGFR immunoreactivity in the different regions of the neocortex of the rat. EGFR immunoreactivity in the neocortex of the rat followed very different patterns according to postnatal ages and cortical areas. EGFR-immunoreactive cells appeared only in dorsal endopiriform cortex at P0. The first EGFR-immunoreactive cells were observed in the neocortex at P3. In the cingulate cortex, the first EGFR-immunoreactive cells appeared at P10. Also, in the retrosplenial cortex, these cells appeared in the agranular region at P3, and in the granular region at P20. These cells were most abundant in the parietal cortex at P90. In adult, the most prominent EGFR immunoreactivity occured in layer IV, V and VI. These cells were numerous in the frontal and parietal cortex, diminishing laterally towards the insular cortex. The intensity of the immunoreaction at P10 was similar to their adult pattern, but their morphologies were exhibited immature features. EGFR immunoreactivity was not found in the glial cells. The present results showing EGFR immunoreactivity is widely distributed in the postnatal developing (except P0) and adult cerebral cortex, mainly localized in neurons. These findings suggest that many growth factors may interact via the EGFR, therefore, actions to promote the proliferation and survival of neurons in the normal postnatal developing neocortex of the rat.