Frontal-lobe activation during semantic memory performance was examined using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing neural activity associated with cognitive function. Left inferior prefrontal cortex was more activated for semantic than for perceptual encoding of words, and for initial than for repeated semantic encoding of words. Decreased activation for semantic encoding of repeated words reflects repetition priming, i.e., implicit retrieval for memory gained in the initial semantic encoding of a word. The left inferior prefrontal region may subserve semantic working memory processes that participate in semantic encoding and that have decreased demands when such encoding can be facilitated by recent semantic experience. These results demonstrate that fMRI can visualize changes in an individual's brain function associated with the encoding and retrieval of new memories.