Different patterns of prefrontal activation are commonly found in studies of episodic and source memory (typically anterior and lateral) compared to those found in studies of autobiographical memory (typically ventromedial). We investigated a proposal that the former pattern reflects contextual interference when retrieving events that occurred in similar contexts. We used virtual reality to simulate contextually varied life-like events, in which subjects received distinct objects from a number of people in a number of locations. We compared fMRI data from two experiments in which the number of events per context varied. The first experiment (Burgess, N., Maguire, E.A., Spiers, H.J., and O'Keefe, J. 2001. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. Neuroimage 14, 439-453) involved 16 objects received from one of two people in one of two locations. The second experiment involved 20 objects, each received from a different person in a different location. The first experiment showed extensive bilateral activation of anterior and lateral prefrontal cortex, as well as a medial temporal and parietal network characteristic of both autobiographical and episodic memory. In the second study, the prefrontal activations were largely absent, while the medial parietal and temporal activations remained, and a ventromedial prefrontal area was additionally activated. Direct comparisons revealed large areas of significantly reduced activation in BA10, with lesser reductions in lateral prefrontal regions. We suggest that involvement of these prefrontal regains in episodic and source memory reflects the use of paradigms involving many events and few sources rather than any fundamental processing requirement of contextual retrieval in the absence of interference.