Beta-endorphin is a neuroendocrine peptide, with morphine-like effects, produced by anterior pituitary, cells of the immune system, and synovial cells. The clinical significance of Plasma Beta-endorphin was investigated in a well characterized cohort of 20 RA patients and 10 healthy controls. Beta-endorphin extraction and concentration were carried out according to Wardlaw. Plasma Beta-endorphin assay was measured as described by Naber. Plasma Beta-endorphin levels in severe RA patients were significantly lower (16.1+/-6.2 pg/ml) than in mild RA patients (45.4+/-2.8 pg/ml), P<0.0001. The mean serum levels of Beta-endorphin were also significantly lower in both RA groups than those in normal controls (62.1+/-5.7 pg/ml), P<0.001. The results indicate that there is an inverse correlation with the plasma Beta-endorphin levels, the rheumatoid disease activity score, and the duration of RA. The depressed plasma Beta-endorphin in patients with RA may be used as an indicator of the disease activity.