We have presented data showing apoptosis is suppressed by dexamethasone in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE) without affecting the generation of free radicals or lipid peroxidation. We examined the effects of dexamethasone on an apoptosis related gene (bcl-2) and on glial cells as marked by glial fibrillary acid protein (GFAP) immunostaining.Model: 7 day old rat pups underwent unilateral carotid artery ligation and exposure to 8% oxygen for 2.5 hours. Animals were pretreated with dexamethasone (0.1 mg/kg) or vehicle. Measurements: Northern blot, Western blot, immunohistochemistry. Results: Bcl-2 expression is elevated in dexamethasone-treated animals compared to vehicle-treated animals at 1 hour after HIE (p = 0.02). Differences were not discernable at 6 and 24 hours post-HIE. Bcl-2 protein was not significantly greater in dexamethasone-treated animals over vehicle-treated animals by Western blot but immunohistochemistry showed preserved bcl-2 staining in dexamethasone-treated animals. Despite no difference in peroxynitrite exposure GFAP immunoreactivity is markedly diminished in dexamethasone-treated animals. Conclusion: Preserved bcl-2 transcription and translation is associated with neuronal survival following HIE further supporting the role of apoptosis as a mechanism of cell death in HIE. GFAP immunoreactivity, a marker of glial cell activation following HIE, is also associated with the dexamethasone neuroprotective effect despite apparent equal exposure to peroxynitrite, a marker of nitric oxide production -an inducer of GFAP. Glial cells may play an important role in apoptosis following HIE. (Supported by the Heart and Stroke Foundation of Canada, the Medical Research Council of Canada, the Ackman Travelling Scholarship, University of Melbourne, Australia).