OBJECTIVE To elucidate the pathophysiological role of adrenomedullin (AM) in rheumatoid arthritis (RA), plasma AM concentration was measured in patients with RA and in healthy contols. The concentration of AM in joint fluid, synovial tissue, and articular cartilage of patients with RA and osteoarthritis (OA) were measured and compared. METHODS Twenty-six patients with RA (aged 62 +/- 4 yrs, all female), 10 healthy controls (aged 57 +/- 5 yrs, all female), and 10 patients with OA (aged 68 +/- 8 yrs, all female) were studied. We measured plasma levels of total and mature AM by immunoradiometric assay and levels of AM in joint tissue by radioimmunoassay. RESULTS Plasma levels of AM in patients with RA (18.35 +/- 6.9 fmol/ml) were found to exceed those in healthy controls (11.64 +/- 2.8 fmol/ml). Moreover, plasma AM showed a significant positive correlation with plasma C-reactive protein (CRP). The correlation coefficient of total AM was 0.685, and that of mature AM was 0.624. Similarly, AM levels in synovium and joint fluid in patients with RA were significantly higher than in OA. In contrast, AM levels in articular cartilage were found to be low, with no significant difference in levels between patients with RA and OA. CONCLUSIONS The relation between plasma AM levels and plasma CRP in patients with RA suggests that plasma AM levels increase with the activity of RA. Moreover, AM levels in synovium and joint fluid of patients with RA were significantly higher than those of patients with OA. Thus, AM probably plays a part in the regulation of the inflammatory process of RA.