A PET study of 10 normal males was carried out using the bolus H 2 15 O intravenous injection technique to examine the effects of picture naming and semantic judgment on blood flow. In a series of conditions, subjects (1) passively viewed flashing plus signs, (2) noted the occurrence of abstract patterns, (3) named animal pictures, or (4) carried out a semantic judgment on animal pictures. Anticipatory scans were carried out after the subjects were presented with the instructions but before they began the cognitive task, as they were passively viewing plus signs. Our results serve to clarify a number of current controversies regarding the neural substrate of picture naming. The results indicate that the fusiform gyrus is unlikely to be the region where low-level perceptual processing such as shape analysis is undertaken. In fact, our evidence suggests that activation of the fusiform gyrus is most likely related to visual perceptual semantic processing. In addition, the inferior/middle frontal lobe activity observed while performing the picture naming and semantic judgment tasks does not appear to be due to the effects of anticipation or preparation. Furthermore, there appears to be a set of regions (a semantic network) that becomes activated regardless of whether the subjects perform a picture naming or semantic judgment task. Finally, picture naming of animals did not activate either parietal regions or anterior inferior left temporal regions, regardless of what subtraction baseline was used.