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OBJECTIVE: The authors’ goal was to test the hypothesis of extrastriatal D2 receptor selectivity as the mechanism of action of clozapine. METHOD: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D2 receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [11C]raclopride was used for determination of D2 receptor occupancy in the striatum. The radioligand [11C]FLB 457 was chosen for determination of D2 receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex. RESULTS: In patients treated with haloperidol the D2 receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D2 receptor occupancy was relatively low in both the striatum and the extrastriatal regions. CONCLUSIONS: The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine.