We used event-related fMRI (ER-fMRI) to test the hypothesis that metaphors bias cognitive processing of semantic relatedness towards a search for a wider range of associations. Twelve right-handed male volunteers read a mixture of metaphoric and literal sentences, each sentence being followed by a single word, which could be semantically related or not to the preceding sentence context. We found that judging unrelated words as contextually irrelevant was associated with increased blood oxygenation level-dependent (BOLD) signal in the right ventrolateral prefrontal cortex in the metaphoric but not in the literal condition. The same region was also activated when subjects endorsed a semantic relation between words and metaphoric sentence primes but not between words and literal sentence primes. We argue that these results are consistent with the notion of semantic open-endedness, whereby figurative statements bias cognitive processing towards a search for a wider range of semantic relationships compared to literal statements, and thus lend further support to the view that coarse semantic coding occurs preferentially in the right hemisphere. (Argyris Stringaris et al.).