The posterior cingulate cortex (PCC) has recently been implicated in the pathophysiology of schizophrenia, through both animal and human studies. We have recently shown abnormal glutamate, GABA, and muscarinic receptor binding in the PCC in schizophrenia. In addition, there is evidence for an abnormal endogenous cannabinoid system in schizophrenia. The endogenous cannabinoid system, including CB1 receptors, is proposed to play a role in modulating neurotransmission via affecting the release of a variety of neurotransmitters, (e.g. GABA). In the present study, we used quantitative autoradiography to investigate the binding of [(3)H]CP-55940 to CB1 receptors in the PCC in schizophrenia subjects compared to controls. A significant 25% increase in CB1 binding was found in the superficial layers (layer I, II) of the PCC of schizophrenia subjects compared to controls, none of whom had recently used cannabis. There was no statistical difference in CB1 binding in the deeper layers (layers III-VI) between the two groups. There were no significant correlations between CB1 binding density and age, PMI, pH, brain weight, freezer storage time, or final recorded antipsychotic drug dose. These results show an increase in CB1 receptor density in the PCC in schizophrenia, and therefore provide support for a role of the endogenous cannabinoid system in schizophrenia.