INTRODUCTION: Some electrophysiological aspects of the interictal activity in temporal lobe epilepsy (TLE) are under debate. However, surgery is often guided by both, pre and intra operative recordings of interictal activity. Some of these studies include intraoperative electrocorticography (ECoG) that guide tailored resection. OBJECTIVE: To analyze several aspects of interictal activity recorded by ECoG and to explore its electrophysiological basis in vitro. PATIENTS AND METHODS: ECoGs from thirteen patients suffering drug resistant TLE were analyzed. Both linear and non linear methods were introduced to explore the ECoG signals. In two cases, neocortical tissue was also electrophysiologically studied in vitro. RESULTS: Interictal ECoG activity showed a mesial origin, a cortical origin or a mixed mesial/temporal origin. Both in cortical and mesial/cortical origin, cortical interictal ECoG signals are characterized by spatiotemporal clusters of activity. In vitro study of cortical tissue from these clusters showed alterations in the synaptic control of excitability. CONCLUSION: Our results suggest an electrophysiological basis of interictal activity. Combination of linear and non linear methods is a very useful tool to explore on line the interictal ECoG activity during surgery.