A relationship between rheumatoid arthritis (RA) and endocrinological abnormality has been suspected for many years. In the present study, we immunohistologically identified the presence of methionine-enkephalin (Met-enk) and leucine-enkephalin (Leu-enk), in synovial tissues collected from RA patients and determined the amount of these peptides and interleukin 1 beta (IL-1 beta) in the culture supernatant of tissue explants by RI and ELISA. Synovial membrane samples obtained by biopsy during artificial joint replacement and plasma samples simultaneously collected from 11 RA patients (11 joint) diagnosed as having classic or definite RA according to the diagnostic criteria of the American Rheumatism Association were used. All 11 patients were females and aged between 36 and 64 years (mean: 45.8 years). As a result of immunohistological standing (ABC method), Met-enk was detected in vascular endothelial cells and Leu-enk in superficial cells, vascular endothelial cells and interstitial cells. Leu-enk concentrations (42.3 +/- 15.8 pg/ml) were higher in the culture supernatant of the synovial membrane than in the plasma (20.7 +/- 13.3 pg/ml). Furthermore, in the culture supernatant the concentration of Leu-enk was positively correlated with that of IL-1 beta (r = 0.789). These findings suggest that Met-enk and Leu-enk are locally produced by synovial tissues and may exert an immunological and/or inflammatory role in RA synovitis.