Although the prefrontal cortex and regions of the medial temporal lobe are commonly co-activated in neuroimaging studies, their precise respective contributions to human memory remain unclear. In this event-related fMRI study, conditions requiring volunteers to simply look at pictures of abstract art were compared with conditions in which they were explicitly instructed to remember similar stimuli for later recognition. Looking, with no explicit instruction to remember, was associated with significant increases in signal intensity in the medial temporal lobe in 19 of the 20 volunteers scanned, but not in a region of the mid-ventrolateral prefrontal cortex that has previously been implicated in memory encoding and retrieval. Behavioral data collected outside the scanner on the same task revealed that recognition of these stimuli was, however, above chance. When the task instructions were changed to encourage the volunteers to remember the stimuli, significant increases in signal intensity were observed bilaterally, in the mid-ventrolateral frontal cortex, but there was no concomitant increase within the medial temporal lobe region. Moreover, behavioral data collected outside the scanner confirmed that recognition of these stimuli was significantly improved relative to the 'just look' trials. These results suggest that the mid-ventrolateral frontal cortex and the medial temporal lobe region make dissociable contributions to human memory that correspond closely to 'top-down' and 'bottom-up' notions of cognitive control, respectively.