P300 is an event-related potential elicited by infrequent target events whose amplitude is dependent on the context provided by the immediately preceding sequence of stimuli, suggesting its dependence on working memory. We employed magnetic resonance imaging sequences sensitive to blood oxygenation level to identify regional changes evoked by infrequent visual target stimuli presented in a task typically used to elicit P300. Targets evoked transient event-related activation bilaterally in the middle frontal gyrus, in the inferior parietal lobe, and near the inferior aspect of the posterior cingulate gyrus beginning within 1.5 s of target onset and peaking between 4.5 and 6 s. These regions have been identified in previous neuroimaging studies in humans, and in single-unit recordings in monkeys, as components of a neural system mediating working memory, which suggests that this system may be activated by the same events that evoke P300.