Recent functional neuroimaging strategies have evaluated cerebral blood flow (CBF) to determine specific sites of action of pharmacologic agents. Since many pharmacologic agents change global CBF, we investigated the effects of global CBF changes on regional perfusion with acetazolamide, which increases global CBF via non-neuronal mechanisms. We used the [15O]PET technique to measure CBF before and after we infused 8 schizophrenic patients and 10 healthy control subjects with acetazolamide. The rostral anterior cingulate cortex demonstrated a greater perfusion increase in the schizophrenic subjects after acetazolamide infusion, relative to other areas of the brain. During the baseline condition, this area showed relative hypoperfusion in our sample of schizophrenic subjects, consistent with previous functional neuroimaging studies. The results demonstrate the need for caution in interpreting CBF changes after pharmacologic challenge, because global CBF changes can confound the assessment of regionally-specific pharmacologic action.