The objective of the present study was to compare brain activation in patients with obsessive-compulsive disorder (OCD) who received pharmacotherapy (selective serotonin reuptake inhibitor (SSRI) or a SSRI-risperidone combination) with that in healthy controls using Tc-99m-hexamethyl propyleneamine oxime (HMPAO) brain single photon emission tomography (SPECT). Twelve OCD patients achieving clinical response (seven SSRI responders, five patients responded to SSRI plus risperidone) underwent post-treatment SPECT scan. The baseline regional cerebral blood flow (rCBF) was significantly reduced in a large part of the cerebral cortex and the left cingulate gyrus in OCD patients compared with controls. After a 50% reduction of the OCD symptoms, bilaterally increased rCBF in the thalamus showed a significant effect of time in both of the patient groups. In the remitted state, although rCBF in the cingulate gyrus did not differ in SSRI responders compared with controls, patients who responded to the combination of SSRI+ risperidone showed significant hypoperfusion in the left anterior cingulate gyrus. SSRI responders had normalized rCBF in the frontal region relative to the control group. Consequently, based on our results, we attribute the observed thalamic rCBF alteration to SSRI treatment. Our results also suggested that brain perfusion changes associated with clinical remission may differ across patient subgroups. (C) 2012 Elsevier Ireland Ltd. All rights reserved.