Recent studies have demonstrated that immune cell-derived β-endorphin inhibits peripheral nociception. Changes in the β-endorphin content of peripheral blood mononuclear cells (PBMC) were also reported in various human disorders. These findings suggest the modulation of pain by immuno-neural interaction through opioid-dependent mechanisms. The aim of this study, therefore, was to determine whether the levels of β-endorphin in PBMC of patients with complex regional pain syndrome (CRPS) differ from those of healthy subjects. Heparinized venous blood was collected from ten CRPS patients (7 women and 3 men; mean age 39.4 ± 13.0 years) and 13 age-matched healthy volunteers (6 women and 7 men; mean age 38.4 ± 10.8 years). PBMC were separated by density gradient centrifugation. β- endorphin was extracted from the cells in a commercial cell lysis buffer and its concentration was measured by enzyme immunoassay technique. Immunoreactive β-endorphin levels in PBMC from the CRPS patients were significantly lower than those from the healthy volunteers (101.5 ± 57.5 versus 222.1 ± 77.6, P < 0.001), and were not correlated to the present pain intensity or pain duration. The results indicate an altered condition of the immune-linked opioid system underlying CRPS. Further immunological approaches may provide new insight into the pathophysiology of CRPS.