AbstractThe presentation of rare target stimuli results in P300 scalp event‐related potentials (ERPs). Generators of this ERP component were found in various brain areas, indicating that multiple cortical and subcortical areas subserve target detection. One of these structures is the mediotemporal lobe (MTL). In the hippocampus, large negative MTL‐P300 potentials are usually observed, whereas reports concerning the rhinal cortex and subiculum are inconsistent. The aim of the present study was to investigate the topography of the mediotemporal P300. ERPs were recorded in epilepsy patients from multicontact depth electrodes, implanted along the longitudinal axis of MTL. Patients had to respond to rare visual target stimuli by a button press. ERP data from the nonfocal hemisphere of 53 patients were included in the analysis. Target detection resulted in large MTL‐P300 potentials in the hippocampus and subiculum. Their latencies did not differ. The hippocampal P300 amplitude increased linearly from anterior to posterior hippocampal body (HB). In contrast, an inverse gradient with larger mean amplitudes in anterior parts was observed for the subiculum. Our results indicate two separate generators of the MTL‐P300, one in the anterior subiculum and one in the posterior HB. Since latencies did not differ, a parallel activation via the entorhinal cortex might have initiated the simultaneous MTL‐P300. Hippocampus and subiculum are essential parts of the MTL‐memory system. Their function within target detection might be to maintain a template of previous stimuli for a comparison with incoming sensory stimuli. © 2009 Wiley‐Liss, Inc.