1. A high oxygen atmosphere induced apoptosis in cultured neuronal cells including PC12 cells and rat embryonic cortical, hippocampal, and basal forebrain neurons associated with DNA fragmentation and nuclear condensation. 2. The sensitivity of CNS neurons to a high-oxygen atmosphere was the following order; cortex > basal forebrain > hippocampus. 3. Cycloheximide and actinomycin-D inhibited the apoptosis, indicating that it depends on new macromolecular synthesis. In contrast, cultured postnatal CNS neurons were resistant to oxidative stress. 4. Neurotrophic factors such as nerve growth factor (NGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) blocked the apoptosis induced by a high-oxygen atmosphere.