Human temporal lobe epilepsy and experimental models of this disease are associated with loss of neurons and other structural alterations in several limbic brain structures including the hippocampal formation and adjacent parahippocampal cortical areas. The goal of this study was to test the hypothesis that seizure activity can produce damage to the retrosplenial granular b cortex (Rgb) which is known to be strongly connected with other limbic structures implicated in epilepsy. To test this hypothesis, we estimated, using stereological methods, the volumes and total neuronal numbers in Rgb cortex of rats that had experienced prolonged status epilepticus induced by pilocarpine (350 mg/kg), rats treated with six electroshock seizures (the first five seizures were spaced by 24-h intervals, whilst the last two were only 2 h apart), and control rats. Adult male Wistar rats were used in this experiment. Status epilepticus produced significant loss of neurons in Rgb cortical layers IV (22%) and V (44%), which was accompanied by volume reductions in layers I (17%), IV (11%), V (18%) and VI (24%). In electroshock-treated rats, the volume of Rgb cortical layer VI was reduced by 17% and the number of neurons estimated in layer V was smaller by 16% relative to control rats. Thus, the finding that status epilepticus and administration of brief generalized seizures both lead to degenerative morphological alterations in Rgb cortex provides the first experimental support for the hypothesis that this cortical area can be involved in seizure activity, as suggested by its anatomical connections.