Enkephalinase (endopeptidase 24.11) is a metallopeptidase that is able to cleave not only neuropeptides and hormones but also immune mediators. The enzyme was quantified in synovial fluid obtained from 36 swollen joints. Its concentration correlated with the synovial fluid cell count, mainly the polymorphonuclear cells and lymphocytes, and with the erythrocyte sedimentation rate. No statistically significant difference in enkephalinase levels was demonstrated between the groups of patients with rheumatoid arthritis, seronegative spondylarthropathy, microcrystalline arthritis, or osteoarthritis. The presence of enkephalinase in the synovial fluid could reflect the intensity of the inflammatory process, or it could represent a physiologic regulator of inflammation and pain within the joint. cleaving not only enkephalins but also a series of other peptides and hormones, such as the chemotactic peptide FMLP, substance P, neurotensin, glucagon, cholecystokinin octapeptide, gastrin, and atrial natriuretic peptide. It is anchored in the plasma lipid membrane bilayer of many normal cell types and tissues (e.g., brain, lung, kidney, bone, thyroid, salivary glands) (1).Although the enzyme is primarily a membranebound protein, a soluble form has been identified in serum and has been shown to be increased in patients with sarcoidosis (2), adult respiratory distress syndrome (3), and end-stage renal failure (4). The cellular origin of this circulating enkephalinase remains unknown. In view of the strong circumstantial evidence implicating substrates of enkephalinase in the local neurogenic mechanism for arthritis (3, enkephalinase appears potentially capable of modulating pain, inflammation, and the biological responses to various hormones and cytokines in the joint.The present study was undertaken to determine whether enkephalinase could be detected in the joints of patients with various clinical forms of arthritis, and consequently, which parameters influence the concentration of this enzyme.Patients and methods. Thirty-six patients (mean * SD age 56.4 -+ 13.4; ma1e:female ratio 0 . Q each of whom had a swollen knee, were included in this study. The diagnoses were as follows: rheumatoid arthritis (n = 13), microcrystalline arthritis (n = lo), seronegative spondylarthropathy (n = 7), and osteoarthritis (n = 6). Synovial fluid was aspirated from the knee joints and immediately analyzed for the presence of crystals and cell count. Blood samples were also obtained for analysis, which included the erythrocyte sedimenta-