The Wisconsin Card Sorting Test (WCST) has been argued to be a sensitive indicator of frontal lobe function. However, several recent studies have failed to find a consistent relationship between structural damage to this cortical area and perseveration on the test. In the present study, positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose was used to examine the relationship of regional brain metabolism to perseverative responding on the WCST in patients with a history of closed-head injury. An inverse relationship was found between perseverative responses and metabolism in the right, but not the left, dorsolateral prefrontal cortex and caudate nucleus. Perseverative responding was not related to metabolism in several other regions of the frontal lobes and basal ganglia, including the putamen and the frontal poles bilaterally. These data suggest that the functional integrity of the right dorsolateral frontal-subcortical circuit is critical for WCST performance.