To determine the exact role of TGF-alpha in glial activation after traumatic brain injury, we investigated the astroglial and microglial responses after cortical stab wound injury in TGF-alpha overexpressing mice. Adult male B6D2-TgN (MMTVTGFA) 29RjC transgenic mice were used for the subjects. This transgenic line carries a TGF-alpha cDNA under the control of the dexamethasone-inducible MMTV promoter. Thus, exogenous administration of dexamethasone induces TGF-alpha overexpression. Male B6D2F1/J mice at the same age served as wild-type animals. After the cortical stab wound injury, expression of glial fibrillary acidic protein, CD-11b and interleukine-6 were investigated immunohistochemically. The results indicate that TGF-alpha might affect astrocytic hypertrophy without affecting microgliosis not only in the normal condition, but also in the pathological condition. Moreover, overexpression of TGF-alpha induced obvious expression of IL-6 around the lesion. This fact might indicate possible role of TGF-alpha in affecting neuronal function.