There is evidence that cortico-striato-thalamo-cortical pathways are involved in the pathophysiology of Tourette syndrome. During the performance of neuropsychological tests in subjects with Tourette syndrome there are suggestions for increased activity in the sensimotor cortex, supplementary motor areas, and frontal cortex. To replicate findings, the authors examined 22 medication-naive children with Tourette syndrome only, 17 medication-naive children with Tourette syndrome and comorbidity, and 39 healthy controls with functional magnetic resonance imaging (MRI). There were no differences in activation in brain regions between the children with Tourette syndrome (divided according to the presence of comorbidity) and healthy controls after correction for the confounders age, sex, and intelligence. Activation in the cingulated gyrus, temporal gyrus, and medial frontal gyrus was correlated significantly with obsessive-compulsive disorder score. The authors did not find significant correlations between activation patterns and age, sex, duration of disease, intelligence, severity of tics, and attention-deficit hyperactivity disorder (ADHD) score.