Regional cerebral blood flow was examined during multiple-trial learning in healthy volunteers. On the basis that incremental learning from trial to trial is severely impaired in neuropsychological studies of patients with medial temporal lesions, we predicted that medial temporal activation might be particularly associated with incremental gains in learning. On the other hand, we predicted that frontal activations would not show any increase during incremental learning, and might even diminish. PET recordings were undertaken while subjects were presented visually with a 15-word list in one of three conditions: a list in which a single word was repeated 15 times (S), a list of novel words (N), and a list which was repeated from before (R). We demonstrated that statistically significant incremental learning did occur when word lists were repeated in (R) trials. The subtraction of novel minus repeated conditions (N-R) was associated with left medial temporal as well as left prefrontal activations, whereas the opposite (R-N) subtraction gave rise to right prefrontal and precuneal activations. In particular, incremental learning during the repeated trials (R) identified a left medial temporal activation, as predicted, but the left frontal activation was no longer evident. We suggest that the left medial temporal region is not only activated by novel, to-be-learned stimuli, but it also contributes to incremental learning as part of a network involved in 'binding' or 'consolidating' new memories. The right frontal and precuneal regions, which participate in the repeated retrieval and rehearsal of already learned memories, are also involved in this network. The left frontal region is implicated in the more 'effortful' or elaborative aspects of memory.