Immunocytochemical markers of specific rat hippocampal interneuron subpopulations, including the calcium binding proteins parvalbumin (PV), and calretinin (CR) were examined in relation to the evolution of spontaneous seizures after electrically induced status epilepticus (SE). PV/CR/NeuN immunoreactive neurons were counted in the hippocampal formation at different time intervals after SE and related to spontaneous hippocampal discharge activity. Decreased PV immunoreactivity was observed within 1 day after SE in the hilus, pre- and parasubiculum, and in the entorhinal cortex layers II and V/VI. In layer III, the density of detectable PV immunoreactive neurons did not decrease significantly, whereas the number of surrounding principal neurons was extensively decreased within a week in most post-SE rats, and after 3-4.5 months in all rats that had developed a progressive evolution of seizures. CR immunoreactive neuron number decreased in all hippocampal subregions except for the stratum lacunosum-moleculare and the EC layer II, in which the density did not decrease significantly. The apparent decrease in the number of PV and CR immunoreactive hilar neurons was correlated with the duration of the SE and was most extensive in rats with a progressive form of epilepsy. The loss of CR and PV expression or the loss of CR- and PV-containing neurons in specific regions of the hippocampal formation may play a role in the progressive nature of epilepsy possibly via increasing the entorhinal-hippocampal activity.