Nine normal volunteers performed a 'theory of mind' task while their regional brain blood flow pattern was recorded using the PET [15O]H2O technique. Control conditions induced subjects to attend to the visual and semantic attributes of known objects. In a third condition, subjects had to infer the function of an unfamiliar object from its form. In the 'theory of mind' condition, subjects had to infer function based on the form of both familiar and unfamiliar objects and in addition, model the knowledge and rationality of another mind about the function of these objects. Performance during the 'theory of mind' condition evoked the activation of a distributed set of neural networks with prominent activation of the left medial frontal lobe (Brodmann area 9) and left temporal lobe (Brodmann areas 21, 39/19, 38). This result suggests that when inferential reasoning depends on constructing a mental model about the beliefs and intentions of others, the participation of the prefrontal cortex is required. When access to such knowledge is affected by central nervous system dysfunction, such as that found in autism, modeling other minds may prove difficult.