The lateral distribution of the P300 component of the event-related brain potential (ERP) was studied in five epileptic patients whose corpus callosum had been surgically sectioned and in seven neurologically intact controls. The P300 was elicited in an auditory “oddball” task using high- and low-pitched tones and in a visual oddball task in which target words were presented either to the left or right visual fields, or to both fields simultaneously. Commissurotomy altered the normal pattern of bilaterally symmetrical P300 waves over the left and right hemispheres, but in a different manner for auditory and visual stimuli. The auditory P3 to binaural tones was larger in amplitude over the right than the left hemisphere for the patients. In the visual task, the laterality of the P300 varied with the visual field of the target presentation. Left field targets elicited much larger P300 amplitudes over the right than the left hemisphere, as did bilateral targets. In contrast, right field targets triggered P300 waves of about the same amplitude over the two hemispheres. The overall amplitude of the P300 to simultaneous bilateral targets was less than the sum of the individual P300 amplitudes produced in response to the unilateral right and left field targets. These shifts in P300 laterality argue against the view that the P300 is an index of diffuse arousal or activation that is triggered in both hemispheres simultaneously irrespective of which hemisphere processes the target information. The results further demonstrate that the P300 does not depend for its production on interhemispheric comparisons of information mediated by the corpus callosum, as suggested recently by Knight et al. (1989).