Alterations of DNA transcription in epilepsy have been shown for a number of ion channels and key enzymes. However, protein translation and especially post-translational modifications enormously impact protein function. Therefore, we analyzed the hippocampal proteome of control and epileptic rats. A prolonged status epilepticus was induced by pilocarpine injection and the hippocampal specimen were prepared during the chronic stage of recurrent seizures four weeks after pilocarpine treatment. Two- dimensional gels gave well reproducible results with on average around 1300 spots on each gel. Differentially expressed protein spots were detected by densitometry and subsequently identified by MALDI TOF mass spectrometry. In particular, we found a significant increase of phosphatidylethanolamine-binding protein (PEBP) and complexin-2 as well as a significant decrease of a- synuclein. These and further yet unidentified proteins may be relevant for the pathogenesis of epilepsy. With this proteomic approach we aim at uncovering the altered protein cascades of ion channel associated function and deciphering key enzymes.