Positron Emission Tomography (PET) imaging of regional cerebral blood flow (rCBF) provides an in vivo method for studying brain function. We used [15O]H20 PET to assess the effect of antipsychotic medications on rCBF in 17 subjects with schizophrenia. Each subject was scanned while receiving antipsychotic medication, and after having been withdrawn from antipsychotic medication for a 3-week period. The two scans were subtracted from one another, using a within subjects design, and the areas of difference were identified using the Montreal method. Subjects treated with antipsychotic medication had significantly higher rCBF in the left basal ganglia and left fusiform gyrus compared with the "off-medication" condition. Significantly higher relative rCBF in the anterior cingulate, left dorsolateral and inferior frontal cortex, and left and right cerebellum was observed when off antipsychotic medication. Upregulation of dopamine D2 receptors may lead to a regional increase of blood flow and metabolism in the basal ganglia, which may explain recently reported anatomical enlargement in these regions.