The neurotoxicant 3,3'-iminodipropionitrile (IDPN) induces a persistent neurological syndrome and an axonopathic condition. In this study, the concentration of glial fibrillary acidic protein (GFAP), measured by solid-phase radioimmunoassay in brain tissue homogenates, was used as a marker of the reactive gliosis occurring in the central nervous system after IDPN intoxication. Male Long-Evans rats were given 3 daily i.p. injections of 0-600 mg/kg/day of IDPN in saline. Seven days after 3 X 400 mg/kg/day, GFAP increases were observed in pons-medulla, midbrain, olfactory bulbs and cerebral cortex, but not in cerebellum, hypothalamus, hippocampus and striatum. Dose-dependent increases in GFAP were observed in the cortex at 10 days after administration, whereas no GFAP response was observed in the cerebellum of the same animals. GFAP increases were obtained in either cingulate, frontal, parietal and occipital-temporal cortical areas 10 days after 3 X 400 mg/kg/day. A large effect was also observed in olfactory bulbs at the same dose and time. The effect of the 3 X 400 mg/kg/day treatment on cingulate cortex GFAP was observed to have a rapid onset, with a peak around one week, and a recovery to basal levels within two weeks after administration. The present results demonstrate region specific, dose- and time-dependent increases in GFAP in the CNS of rats exposed to IDPN.