Receptor binding has been examined region by region in both in vitro and in vivo studies, but less attention has been paid to the connectivity of regional receptor binding despite the fact that neurophysiological studies have indicated an extensive inter-regional connectivity. In this study, we investigated the connectivity of regional dopamine D2 receptor binding in positron emission tomography data from 10 drug-naive patients with schizophrenia and 19 healthy controls. We applied a structural equation method to regional receptor binding. The results indicated that the network models of the patients and normal subjects were significantly different. As to the individual path coefficients, (a) connectivity between cortical regions was different between groups; (b) connectivity from the prefrontal cortex, parietal cortex, and thalamus to the anterior cingulate differed from that in controls; and (c) connectivity from the prefrontal cortex to the anterior cingulate and thalamus via the hippocampus was observed in normal subjects but not in patients. These results suggest that a systems-level change reflected in the connectivity of D2 receptor binding is present in schizophrenia.