Background: Molecular imaging of dopaminergic parameters has contributed to the dopamine hypothesis of schizophrenia, expanding our understanding of pathophysiology, clinical phenomenology and treatment. Our aim in this study was to compare 18F-fallypride binding potential BPND in a group of patients with schizophrenia-spectrum illness vs. controls, with a particular focus on the cortex and thalamus. Methods: We acquired 18F-fallypride positron emission tomography images on 33 patients with schizophrenia spectrum disorder (28 with schizophrenia; 5 with schizoaffective disorder) and 18 normal controls. Twenty-four patients were absolutely neuroleptic naïve and nine were previously medicated, although only four had a lifetime neuroleptic exposure of greater than two weeks. Parametric images of 18F-fallypride BPND were calculated to compare binding across subjects. Results: Decreased BPND was observed in the medial dorsal nucleus of the thalamus, prefrontal cortex, lateral temporal lobe and primary auditory cortex. These findings were most marked in subjects who had never previously received medication. Conclusions: The regions with decreased BPND tend to match brain regions previously reported to show alterations in metabolic activity and blood flow and areas associated with the symptoms of schizophrenia. © 2010 Elsevier B.V.