Case reports, numerous brain imaging studies, and certain disease states suggest that the orbital frontal cortex and the striatum are dysfunctional in obsessive-compulsive disorder (OCD). Interest has also grown recently concerning the genetic, neuroanatomic, and clinical links between OCD, chronic motor tics, and Gilles de la Tourette Syndrome (GTS). To test the hypothesis of possible orbito-frontal/basal ganglia dysfunction in GTS, similar to OCD, we studied 20 unmedicated GTS subjects, 10 of whom also had comorbid OCD (GTS/OCD), and 8 control subjects. The subjects were examined with high-resolution single photon emission computed tomography (SPECT) and the labeled regional cerebral blood flow (rCBF) ligand technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO). As a group, GTS subjects showed significantly elevated right frontal/visual cortex activity (mean = 0.879, SD = 0.107) compared with control subjects (mean = 0.798, SD = 0.049). A subanalysis comparing simple GTS versus GTS with comorbid OCD failed to reveal significant differences in regional flow.