A slowly rising cortical potential shift with negative polarity following the imperative stimulus of a forewarned reaction time task, the ‘post-imperative negative variation’ (PINV), is regularly observed in schizophrenic patients but not in controls. The topography of the PINV suggests that it may originate in frontal cortical regions. We used a task designed to test two putative prefrontal cortical functions: working memory and processing of ambiguity. Nineteen patients with a chronic schizophrenic disorder and 19 control subjects matched for age, sex, and education participated in two experimental sessions. The EEG was recorded from frontal, central, temporal, and parietal leads over both hemispheres using a DC amplifier. PINV amplitudes were generally larger in patients than in controls. If the result of comparing physical features of the two successively presented stimuli (warning and imperative stimulus) was ambiguous rather than clear, an augmentation of the PINV amplitudes was seen in both groups. If this comparison required high rather than low involvement of working memory functions, PINV amplitudes were augmented in schizophrenic patients only. Scalp distribution of the PINV indicated a left-hemisphere fronto-central PINV maximum in patients, and a right-hemisphere predominance in controls, which was larger following ambiguous stimulus comparisons. These results suggest that ambiguity during the comparison of physical features of successively presented stimuli may be a general factor of the PINV in schizophrenic patients and healthy controls. Augmented involvement of working memory functions, presumably subserved by the prefrontal cortex, specifically affected the fronto-centrally predominant PINV in schizophrenic patients. This result is compatible with the hypothesis of prefrontal cortical dysfunctions in schizophrenia.