Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes, a subtype of glia in central nervous system. The hallmark of this response, often terms "reactive gliosis", is the enhanced expression of the major intermediate filament protein of castrocytes, glial fibrillary acidic protein (GFAP). These changes in the astrocytes suggest that GFAP may be a useful biochemical indicator of neurotoxicity. To investigate this possibility, we administered intra-peritoneally prototype nerotoxicants, metharnphetamine (MAP, 5 mg/kg), cocaine (30 mg/kg), N-buthyl benzenesulfonamide (NBBS, 300 mg/kg) and trimethytin (TMT, 8 mg/kg) to Wistar Rats and then assessed the effects of these agents on content of GFAP, which were determined by Sandwish ELISA and evaluated with neurotoxic symptoms, and quantitative changes of imrnunoreactivity of GFAP by light microscopic image analysis in specific regions. We found that assay of GFAP revealed time- and region-dependant patterns of neurotoxicity. The GFAP immunoreactivity of rat brain was increased in substantia nigra and hippocampus by MAP, NBBS and TMT; in roedial septal nucleus and nucleus accurnbens, it was also increased by RrBBS. Sandwich ELISA showed that GFAP levels of cerebrum in all groups on days 3 and 7 and that of brainstem(including cerebellum) in MAP, NBBS groups on day 1 and 3 were increased. A review of the background, design and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.otoxicity.