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 analysed 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. The hippocampal weight did not differ significantly between control (41 ± 8 mg, mean ± SD) and pilocarpine-treated rats (40 ± 9 mg). Cell lysates were produced with comparable total protein amounts between control (3.4 ± 0.4 g/l) and pilocarpine-treated rats (3.6 ± 0.6 g/l). Two-dimensional gels gave well reproducible results with on average around 1200 spots on each gel. Differentially expressed protein spots were detected by densitometric analysis. Proteins will subsequently be identified by MALDI TOF mass spectrometry. With this proteomic approach we aim at uncovering the altered protein cascades of ion channel associated function and deciphering key enzymes in the pathogenesis of epilepsy.