Numerous morphological studies of epileptic brains have been made over the past century. The earliest descriptions were made of brain tissue obtained from humans with epilepsy, whereas the more recent studies have concentrated on the analysis of brain tissue from various animal models in an attempt to gain a better understanding of the basic mechanisms of epileptic activity. A review of the current literature demonstrates that many different animal models have been analyzed with neuroanatomical methods. The most common and consistent cytological finding described in the brains of epileptic humans and animals with experimental focal epilepsy is neuronal loss with concomitant gliosis. In addition, the use of contemporary immunocytochemical methods has demonstrated specific neurochemical changes for various neurotransmitters, most notably for γ-aminobutyric acid (GABA) and its synthesizing enzyme, glutamate decarboxylase (GAD).