Single photon emission computed tomography (SPECT) images were obtained in 10 right-handed neuroleptic-treated schizophrenic patients and 10 healthy volunteers using Tc-99m-hexamethyl-propylenamine oxime (Tc99m-HMPAO) during performance of the Wisconsin Card Sorting Test (WCST) and at rest. None of the patients showed severe impairment on the WCST. The patient group showed a statistically insignificant trend to incur more unique errors. In both the patient and control groups, the left lateral prefrontal blood flow significantly increased during the WCST, as compared to during resting conditions. Only during the WCST, the patient group showed a significant regional cerebral blood flow (rCBF) decline in the left medial prefrontal cortex, as well as in the right side under both the test and resting conditions. This left medial prefrontal rCBF during the WCST correlated positively with the number of unique errors, although this correlation was statistically insignificant. The right fronto-parietal rCBF was significantly increased in the patient group under both the test and resting conditions. Moreover, in the left hippocampal region, the patient group showed a significant rCBF increase under resting conditions.