This study investigated mismatch negativity (MMN) differences between subjects with non-epileptic seizures (NES), subjects with epilepsy, and healthy controls. Event-related potentials (ERPs) were obtained from 14 patients with NES, 15 patients with epilepsy and 16 healthy control subjects. A conventional MMN procedure was used with a random sequence of 12% deviant tones (922 Hz) and 88% standard tones (1000 Hz). Subjects were instructed to ignore the tones delivered through headphones whilst reading a book. Significant differences in distribution of the mismatch negativity (MMN) in patients with NES compared to controls were obtained (F3, p <or= 0.019; Cz, p <or= 0.044) and longer MMN duration in patients with epilepsy compared with patients with NES (p <or= 0.039) was observed. The change that has been analyzed is one of relative (or scaled) amplitude rather than absolute amplitude. These differences observed at Cz/F3 suggest an increase in emphasis of the MMN in the frontocentral region in patients with NES compared to healthy controls, suggesting that the MMN is generated in a different way in NES compared with controls. This could indicate that one of the normal MMN generator areas does not function normally in NES. Increased absolute amplitude of the MMN has previously been observed in anxiety disorders particularly in post-traumatic stress disorder (PTSD). We discuss similarities between NES and PTSD, suggesting that the increased relative amplitude obtained in this study may be related to mechanisms of generation of NES. The prolonged duration of the MMN in epilepsy could be related to difficulties in processes associated with novelty discrimination (closure of MMN generating mechanism). This information processing dysfunction could be associated with the concentration and memory difficulties that are observed in some patients with epilepsy. This study provides electrophysiological evidence of abnormal processing of auditory stimuli in both clinical conditions when compared to healthy controls, and interictal differences between a group of patients with epilepsy and a group of patients with non-epileptic seizures, as measured by the MMN.