This study examined the effects of rehearsal on the neural substrates supporting episodic autobiographical and semantic memory. Stimuli were collected prospectively using audio recordings, thereby bringing under experimental control ecologically valid, naturalistic autobiographical stimuli. Participants documented both autobiographical and semantic stimuli over a period of 6-8 months, followed by a rehearsal manipulation during the 3 d preceding scanning. During functional magnetic resonance imaging scanning, participants were exposed to recordings that they were hearing for the first, second, or eighth time. Rehearsal increased the rated vividness with which information was remembered, particularly for autobiographical events. Neuroimaging findings revealed rehearsal-related suppression of activation in regions supporting episodic autobiographical and semantic memory. Episodic autobiographical and semantic memory produced distinctly different patterns of regional activation that held even after eight repetitions. Region of interest analyses further indicated a functional anatomical dissociation in response to rehearsal and memory conditions. These findings revealed that the hippocampus was specifically engaged by episodic autobiographical memory, whereas both memory conditions engaged the parahippocampal cortex. Our data suggest that, when retrieval cues are potent enough to engage a vivid episodic recollection, the episodic/semantic dissociation within medial temporal lobe structures endure even with multiple stimulus repetitions. These findings support the multiple trace theory, which predicts that the hippocampus is engaged in the retrieval of rich episodic recollection regardless of repeated reactivation such as that occurring with the passage of time.