The early stages of selective neuronal loss occurring in the hippocampus and other brain regions after prolonged epileptic activity have fine structural characteristics matching those induced by excitotoxic agents. NMDA receptor antagonists provide protection against such damage. The extracellular concentration of glutamate or aspartate may be transiently raised prior to or early in seizure activity but tends not to match the levels associated with hypothalamic damage in the original paradigm of excitotoxicity. Various aspects of the excitotoxic process are examined to see if they can account for particular details of the pattern of selective neuronal loss. A full explanation of selective vulnerability will take into account not only a range of characteristics of the vulnerable neuron but also its functional network during sustained activity.