In all signed languages used by deaf people, signs are executed in “sign space” in front of the body. Some signed sentences use this space to map detailed “real-world” spatial relationships directly. Such sentences can be considered to exploit sign space “topographically.” Using functional magnetic resonance imaging, we explored the extent to which increasing the topographic processing demands of signed sentences was reflected in the differential recruitment of brain regions in deaf and hearing native signers of the British Sign Language. When BSL signers performed a sentence anomaly judgement task, the occipito-temporal junction was activated bilaterally to a greater extent for topographic than nontopo-graphic processing. The differential role of movement in the processing of the two sentence types may account for this finding. In addition, enhanced activation was observed in the left inferior and superior parietal lobules during processing of topographic BSL sentences. We argue that the left parietal lobe is specifically involved in processing the precise configuration and location of hands in space to represent objects, agents, and actions. Importantly, no differences in these regions were observed when hearing people heard and saw English translations of these sentences. Despite the high degree of similarity in the neural systems underlying signed and spoken languages, exploring the linguistic features which are unique to each of these broadens our understanding of the systems involved in language comprehension.