The expression of the kappa-opioid receptor on human peripheral blood cells (in rheumatoid arthritis cases and normal volunteers) was examined using reverse transcriptase polymerase chain reaction (RT-PCR), and the relationship between its expression and the inflammatory activity or chronic pain in patients with rheumatoid arthritis (RA) was determined. RT-PCR was performed on the peripheral blood cells obtained from 37 patients with RA and 13 healthy volunteers. kappa-Opioid receptor mRNA expression was exhibited on the blood cells of 37% of RA patients (14/ 37) and 54% of healthy volunteers (7/13) , and the levels of expression were lower in the RA patients than in the healthy volunteers. Regarding the relationship between the expression of kappa-opioid receptor mRNA and the symptoms in RA patients, it was noted that the expression of the receptor mRNA was significantly decreased in RA patients in whom erythrocyte sedimentation rate (ESR), Lansbury index, and visual analogue pain scores were high. The kappa-opioid receptor mRNA was expressed on four cell types, namely, T and B cells, macrophages, and natural killer (NK) cells in RA patients; however, it was expressed only on the T and B cells and macrophages (and not on NK cells) in the healthy volunteers. Our findings suggest that the levels of expression of kappa-opioid receptor mRNA were decreased in RA patients in comparison with those in healthy volunteers; and that they were significantly related to the inflammatory activity or chronic pain in the RA patients. The higher the mRNA expression level, the less severe the inflammatory changes of RA. The kappa-opioid receptor may thus play a role in the modulation of nociception and anti-inflammatory changes in chronic inflammatory disorders.