In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefrontal cortex) and lateral pain system (primary somatosensory cortex) in male volunteers has been quantitated using [11C]diprenorphine and positron emission tomography. High levels of opioid receptor binding were seen in the cortical projections of the medial pain system in the cingulate and prefrontal cortex as has previously been observed in post-mortem studies. However, a focal reduction of opioid receptor binding was observed and quantitated in the primary motor/sensory strip when compared to surrounding parietal cortex. This new finding suggests that the medial pain system is likely to be more susceptible to exogenous and endogenous opioid neuromodulation than the so-called lateral pain system.