In all cognitive tasks, general task-related processes operate throughout a given task on all items, whereas specific item-related processes operate differentially on individual items. In typical functional neuroimaging experiments, these two sets of processes have usually been confounded. Herein we report a combined positron emission tomography and event-related potential (ERP) experiment that was designed to distinguish between neural correlates of task-related and item-related processes of memory retrieval. Two retrieval tasks, episodic and semantic, were crossed with episodic (old/new) and semantic (living/nonliving) properties of individual items to yield evidence of regional brain activity associated with task-related processes, item-related processes, and their interaction. The results showed that episodic retrieval task was associated with increased blood flow in right prefrontal and posterior cingulate cortex, as well as with a sustained right-frontopolar-positive ERP, but that the semantic retrieval task was associated with left frontal and temporal lobe activity. Retrieval of old items was associated with increased blood flow in the left medial temporal lobe and with a brief late positive ERP component. The results provide converging hemodynamic and electrophysiological evidence for the distinction of task- and item-related processes, show that they map onto spatially and temporally distinct patterns of brain activity, and clarify the hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal encoding and retrieval asymmetry.