Transforming growth factor-alpha (TGF-alpha ) and epidermal growth factor receptor (EGFR) immunoreactivities were examined in the cerebral cortex of the rat during postnatal development. TGF-alpha -immunoreactive cells were found at birth in all cortical layers except the molecular layer. TGF-alpha -immunoreactive cells were most abundant in the parietal cortex at P20. The intensity and number of the TGF-alpha -immunoreactive cells increased at postnatal days 15 or 20 (P15 - P20). Mature patterns of TGF-alpha -immunoreactive cells were achieved at P20. EGFR -immunoreactive cells appeared only in dorsal endopiriform cortex at P0. The first EGFR -immunoreactive cells were observed in the neocortex at P3. 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. Adult patterns were reached on and after P10. The time of appearance and localization of EGFR immunoreactivity correlated with functional activity in the different cortical areas. No clear labelling of glial cells with TGF-alpha and EGFR antibodies was found. TGF -alpha and EGFR immunoreactivity was observed in the majority of neurons in the postnatal developing and adult cerebral cortex of the rat. Also double -immunohistochemistry with antibodies to TGF-alpha and EGFR showed co-localization of TGF -alpha and EGFR in neurons of the cerebral cortex. Co-localization of TGF-alpha and EGFR was first detectable in most cortices at P3. By P10, these neurons showed immature neuronal features. The present results showing TGF -alpha and EGFR immunoreactivity is widely distributed in the postnatal developing (except P0) and adult cerebral cortex, mainly localized in neurons. And TGF-alpha and EGFR co-localize in most neurons, thus indicating that most EGFR -containing cells are TGF-alpha -synthesizing cells. In addition to difference of time of appearance and mature neuronal pattern suggest that TGF-alpha has the capacity of activating the EGFR in the normal postnatal developing cerebral cortex, therefore, TGF-alpha and EGFR may interact within cortical neurons through many different mechanism according to postnatal age.