Summary:In the last decade, the recognition of the high frequency of cortical malformations among patients with epilepsy especially children, has led to a renewed interest in the study of the pathophysiology of cortical development. This field has also been spurred by the recent development of several experimental genetic and non-genetic, primarily rodent, models of cortical malformations. Epileptiform activity in these animals can appear as spontaneous seizure activity in vivo, in vitro hyperexcitability, or reduced seizure susceptibility in vitro and in vivo. In the neonatal freeze lesion model, that mimics human microgyria, hyperexcitability is caused by a reorganization of the network in the borders of the malformation. In the prenatal methylazoxymethanol model, that causes a diffuse cortical malformation, hyperexcitability is associated with alteration of firing properties of discrete neuronal subpopulations together with the formation of bridges between normally unconnected structures. In agreement with clinical evidence, these expenmental data suggest that cortical malformations can both form epileptogenic foci and alter brain development in a manner that causes a diffuse hyperexcitability of the cortical network. Key Words: Neocortex-Hippocampus-Development-Neuronal migration-Methylazoxymethanol.As early as the end of the nineteenth century, neuropathologists began to report an association between cortical malformations and epilepsy (1-3). Until recently, however, clinical and experimental research yielded few insights into the pathophysiology of this distinct class of epilepsies. In fact, the last decade has seen three major scientific advances that have directly contributed to the "rediscovery" and renewed interest in examining the cause of epilepsy in patients with cortical malformations: mation and epilepsy. Moreover, neuropathologic analysis of resected tissue has frequently demonstrated the presence of more subtle malformations that were not identified in vivo. 3. Recent progress in human molecular genetics has allowed the identification of several genes whose mutations lead to both malformations and epilepsy. In parallel, several genetic and nongenetic rodent models of cortical malformations were shown to be associated with either spontaneous seizures or hyperexcitability .Our goal is to review the contributions of these animal models to our understanding of the pathophysiology of cortical malformations and to discuss their possible link with epilepsy. CORTICAL MALFORMATIONS IN HUMANSHuman cortical malformations have been the subject of several reviews (4-8) and the histology of the major types of cortical malformations encountered is fairly well established (see Fig. 1). In addition, classification of cortical malformations (based on neuropathology, radiology, etiology, or a combination of these elements) has 811