Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings.