The aim of this study was to investigate plasma adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) level in patients diagnosed with early rheumatoid arthritis (RA). Furthermore, several inflammatory cytokines were measured in those patients to clarify the roles of AM and PAMP. Forty patients diagnosed with early RA (women 46 +/- 8.5 years old) and 10 healthy controls (women 57 +/- 5 years old) were studied. Plasma levels of AM, PAMP, matrix metalloprotease 3 (MMP-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP) were measured using an immunoradiometric assay and enzyme-linked immunosorbent asay (ELISA) methods. The plasma levels of AM (17.5 +/- 8.4 fmol/ml) and PAMP (2.01 +/- 0.57 fmol/ml) in patients exceeded those in healthy controls (AM 8.6 +/- 1.7, PAMP 1.17 +/- 0.34 fmol/ml). Moreover, plasma AM and PAMP levels demonstrated a significantly positive correlation with plasma MMP-3 and IL-6 levels. Nevertheless, CRP and TNF-alpha levels in these patients showed no significant correlation with plasma AM and PAMP levels. These data support the possible role for AM and PAMP in the pathophysiology of early RA.