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The ability to remember the past depends on cognitive operations that are recruited when information is initially encountered. In the current experiment, we investigated neural processes that subserve the memorability of a fundamental class of social information: self-knowledge. Participants evaluated the extent to which a series of personality characteristics were self-descriptive. Brain activation was measured using event-related functional magnetic resonance imaging (fMRI) and contrasted based on: (i) whether each word was later remembered or forgotten; and (ii) whether or not each item was judged to be self-relevant. Results revealed that activity in medial prefrontal cortex predicted both subsequent memory performance and judgements of self-relevance. These findings extend current understanding of the nature and functioning of human memory.