Neuropsychological research has established that the inhibition of dominant response tendencies is a function of the prefrontal cortex. These inhibitory mechanisms are tested using tasks like the Stroop task, in which the prepotency of the dominant response is based on a learned relationship of stimulus and response. However, it has also been reported that patients with prefrontal lesions may have problems inhibiting imitative responses. The question arises of whether the inhibition of overlearned and imitative responses entails the same or different functional mechanisms and cortical networks. In a recent neuropsychological study with prefrontal patients we found first evidence for such a dissociation. The present fMRI study further investigated this question by directly comparing brain activity in the inhibition of overlearned and imitative response tendencies. It emerges that response inhibition in the two tasks involves different neural networks. While the inhibition of overlearned responses requires a fronto-parietal network involved in interference control and task management, the inhibition of imitative responses involves cortical areas that are required to distinguish between self-generated and externally triggered motor representations. The only frontal brain area that showed an overlap was located in the right inferior frontal gyrus and is probably related to the generation of the stop signal.