Prolonged seizures have long been known to be associated with cell injury and cell death in brain. Such seizure-related neuronal injury has been assumed to be mediated by glutamate, the same excitatory amino acid in the central nervous system which propagates the seizure itself. Elevated extracellular concentrations of glutamate have not been demonstrated in brain during seizures in experimental animals. However, these studies have not been performed during status of a duration adequate to induce cell injury, a time when the putative neurotoxins might be demonstrable. We therefore induced status epilepticus (recorded both with conventional surface EEG and with deep electrodes in the area of greatest vulnerability, the piriform cortex) and lengthened the time of status to the point of cell death. Seizures were induced with intravenous kainic acid, and prolonged by injecting the NMDA antagonist AP-7 into the substantia nigra. Microdialysis probes were introduced into the piriform cortex of one hemisphere to assess the presence of extracellular glutamate. In the contralateral hemisphere the degree of neuronal injury was estimated by measurement of heat shock protein (HSP) expression and cell death quantified by acid fuchsin staining. In this model, neuronal injury correlates linearly with seizure duration; however, elevation of glutamate in the extracellular space was not seen even when neuronal injury was profound.