The Wisconsin Card Sorting Test (WCST) is used clinically for evaluating frontal lobe function, but there is some controversy as to its specificity for detecting frontal lobe damage. To investigate the cerebral regions essential to the performance of the Card Sorting Test, we measured the regional cerebral blood flow (rCBF) in 18 normal subjects by PET under the three conditions: (i) during the Modified Card Sorting Test (MCST); (ii) during a matching-to-sample (MTS) task, based on the MCST, but with selective attention to one of three stimulus categories (colour, number or shape) as a control to cancel the effects of maintenance of sets in the MCST; (iii) under resting conditions as overall control. When rCBF during the MCST was compared with that during each MTS task separately, significant activations were observed during the MCST in the left or bilateral dorsolateral prefrontal cortex (DLPFC), bilateral inferior parietal lobes, left superior occipital gyrus and left cerebellum. Compared with all the MTS tasks inclusively, significant increase in rCBF was detected during the MCST in the bilateral DLPFC, inferior parietal lobes, striate cortex, cerebellum and left occipital cortex. These results suggest the involvement of the DLPFC and other related areas such as the inferior parietal cortex in the execution of the MCST, and may help explain why a variety of brain lesions can result in impaired performance on the Card Sorting Test.