The psychological processes through which humans learn a language have gained considerable interest over the past years. It has been previously suggested that language acquisition partly relies on a rule-based mechanism that is mediated by the frontal cortex. Interestingly, the actual structure involved within the frontal cortex varies with the kind of rules being processed. By means of functional MRI we investigated the neural underpinnings of rule-based language processing using an artificial language that allows direct comparisons between local phrase structure dependencies and hierarchically structured long-distance dependencies. Activation in the left ventral premotor cortex (PMC) was related to the local character of rule change, whereas long-distance dependencies activated the opercular part of the inferior frontal gyrus (Broca's area (BA) 44). These results suggest that the brain's involvement in syntactic processing is determined by the type of rule used, with BA 44/45 playing an important role during language processing when long-distance dependencies are processed. In contrast, the ventral PMC seems to subserve the processing of local dependencies. In addition, hippocampal activity was observed for local dependencies, indicating that the processing of such dependencies may be mediated by a second mechanism. Hum Brain Mapp, 2007. © 2007 Wiley-Liss, Inc.