OBJECTIVE: The purpose of the study was to compare regional cerebral blood flow (CBF) in schizophrenic patients never treated with psychotropic drugs (drug-naive) and in schizophrenic patients free from drugs for various amounts of time. METHOD: Seventeen schizophrenic patients (nine who were drug naive and eight who had been drug free for at least 3 weeks) and 12 healthy volunteers were included in the study. Regional cerebral perfusion was studied with the use of a head- dedicated, high-resolution single photon emission computed tomography (SPECT) system. Cerebral SPECT scans were performed with technetium-99m- hexamethyl-propyleneamine oxime as a tracer. Regional CBF was measured as a ratio of regional tracer uptake to either cerebellar or whole brain tracer uptake. RESULTS: When the cerebellum was taken as the reference region, the drug-naive patients showed a significant bilateral reduction of perfusion in the mesial, dorsolateral, and basal prefrontal cortex, in the temporal cortex, and in the subcortical gray structures: thalamus, caudate nucleus, and putamen/pallidum complex. No significant differences emerged in the comparison between the drug-free patients and the healthy subjects. With correction for whole brain activity, some of the differences that had been found disappeared, but a significant hypoperfusion persisted in the basal ganglia and thalamus of the drug-naive, but not the drug-free, patients. Few correlations between symptom presentation and regional CBF perfusion were observed in the schizophrenic patients. CONCLUSIONS: These results suggest a pattern of cerebral hypoperfusion in schizophrenic patients never treated with neuroleptics that was not detectable in patients who had undergone various periods of pharmacological washout.Abstract Teaser