We propose a new hypothesis concerning the lateralization of prefrontal cortex (PFC) activity during verbal episodic memory retrieval. The hypothesis states that the left PFC is differentially more involved in semantically guided information production than is the right PFC, and that the right PFC is differentially more involved in monitoring and verification than is the left PFC. This “production-monitoring hypothesis” differs from the existing “systematic-heuristic hypothesis,” which proposes that the left PFC is primarily involved in systematic retrieval operations, and the right PFC in heuristic retrieval operations. To compare the two hypotheses, we measured PFC activity using positron emission tomography (PET) during the performance of four episodic retrieval tasks: stem cued recall, associative cued recall, context recognition (source memory), and item recognition. Recall tasks emphasized production processes, whereas recognition tasks emphasized monitoring processes. Stem cued recall and context-recognition tasks underscored systematic operations, whereas associative cued recall and item-recognition tasks underscored heuristic operations. Consistent with the production-monitoring hypothesis, the left PFC was more activated for recall than for recognition tasks and the right PFC was more activated for recognition than for recall tasks. Inconsistent with the systematic-heuristic hypothesis, the left PFC was more activated for heuristic than for systematic tasks and the right PFC showed the converse result. Additionally, the study yielded activation differences outside the PFC. In agreement with a previous recall/recognition PET study, anterior cingulate, cerebellar, and striatal regions were more activated for recall than for recognition tasks, and the converse occurred for posterior parietal regions. A right medial temporal lobe region was more activated for stem cued recall and context recognition than for associative cued recall and item recognition, possibly reflecting perceptual integration. In sum, the results provide evidence for the production-monitoring hypothesis and clarify the role of different brain regions typically activated in PET and functional magnetic resonance imaging (fMRI) studies of episodic retrieval.