When task instructions are given, the human brain establishes a task set before the task is actually performed. By introducing a delay between the instruction and the task, we have identified the neural correlates of task sets using functional magnetic resonance imaging (fMRI). Subjects were instructed to remember a sequence of positions or letters, either in the order presented or in the reverse order. Spatial or verbal processing areas were active during the delay, depending on whether positions or letters were to be remembered, whereas the anterior region of the prefrontal cortex (PFC) was active regardless of the domain of the items. Furthermore, the nature of the interaction between the anterior PFC and the domain-specific posterior prefrontal areas (superior frontal sulcus and left inferior frontal gyrus) depended on whether the items were to be remembered in the forward or backward order. Thus we have identified inter-regional interactions that reflect preparation for task performance.