The substantia nigra pars reticulosa (SNpr) is involved in the initiation and propagation of seizures within the limbic system (cingulate and parahippocampal gyri and associated connections in the brain stem, e.g. amygdala, hypothalamus, some thalamic nuclei, and parts of basal ganglia). We have investigated the pattern of neuronal injury (using heat shock protein (HSP) expression) and cell death (acid-fuchsin (AF) staining) in SNpr and limbic structures following seizures evoked by bilateral intranigral injection of kainic acid. Affected cells were observed predominantly in piriform cortex, amygdala, hippocampal formation, and thalamic nuclei; massive necrosis or hemorrhage occurred in bilateral piriform cortices following prolonged seizures. The piriform cortex may play an important role in the activation of limbic seizures under the regulation of the SNpr.