Using functional neuroimaging techniques (PET and fMRI), various cortical, limbic, and paralimbic structures have been identified in the last decade as neural substrates of human emotion. In this study we used a novel approach (intracerebral recordings of event-related potentials) to add to our knowledge of specific brain regions involved in affective picture processing. Ten intractable epileptic patients undergoing pre-surgical depth electrode recording viewed pleasant, neutral, and unpleasant pictures and intracerebral event-related potentials (ERPs) were recorded. A total of 752 cortical and subcortical sites were investigated. Significant differences in ERPs to unpleasant as compared to neutral or pleasant pictures were frequently and consistently observed in recordings from various brain areas--the mesial temporal cortex (the amygdala, the hippocampus, the temporal pole), the lateral temporal cortex, the mesial prefrontal cortex (ACC and the medial frontal gyrus), and the lateral prefrontal cortex. Interestingly, the mean latencies of responses to emotional stimuli were somewhat shorter in the frontal lobe structures (with evidently earlier activation within lateral prefrontal areas when compared to mesial prefrontal cortex) and longer in the temporal lobe regions. These differences, however, were not significant. Additional clearly positive findings were observed in some rarely investigated regions--in the posterior parietal cortex, the precuneus, and the insula. An approximately equivalent number of positive findings was revealed in the left and right hemisphere structures. These results are in agreement with a multisystem model of human emotion, distributed far beyond the typical limbic system and substantially comprising lateral aspects of both frontal lobes as well.