Differentiated neurons were investigated for their susceptibility to oxidative damage based on variations in the oxidant defense system occurring during differentiation. The main antioxidant enzymes and substances in human neuroblastoma (IMR-32) cells were evaluated pre- and post-differentiation to a neuronal phenotype. The activity of CuZn superoxide dismutase (CuZnSOD) and Mn superoxide dismutase (MnSOD) and the concentration of CuZnSOD were higher, but the activity and concentration of catalase were lower after differentiation. Differentiated cells had higher activity of glutathione peroxidase (GPx), lower concentration of total glutathione, a higher ratio of oxidised/reduced glutathione and lower activity of glucose-6-phosphate dehydrogenase than undifferentiated cells. We conclude that differentiated neuronal cells may be highly susceptible to oxidant-mediated damage based on the relative activities of the main antioxidant enzymes and on a limited capacity to synthesise and/or recycle glutathione.