BACKGROUND AND OBJECTIVE Adrenomedullin (AM) is a recently discovered peptide which has potent vasodilatory activity. We have found that the plasma adrenomedullin level is elevated in hyperthyroidism, suggesting a potential role of AM in the decrease of vascular resistance in thyrotoxicosis. Proadrenomedullin, a precursor of adrenomedullin, yields another peptide termed proadrenomedullin-N terminal 20-peptide (PAMP). PAMP also has potent vasodilatory activity. Although the regulation of secretion of AM and PAMP is not fully understood and the mechanism by which the plasma AM level is elevated in hyperthyroidism remains unknown, it is of interest to determine the plasma concentration of PAMP in thyrotoxicosis. DESIGN AND PATIENTS We measured the plasma concentration of immunoreactive AM and PAMP in newly recruited untreated thyrotoxic Graves' patients using specific antibodies to each peptide. RESULTS Not only AM, but also the plasma concentration of PAMP in thyrotoxic patients was significantly (P < 0.01) elevated (4.7 +/- 0.9 pmol/l), compared to that in control subjects (2.6 +/- 0.8 pmol/l). The correlation was marginally significant between the plasma AM concentration and serum free thyroid hormone levels. The plasma PAMP level tended to be more elevated when thyrotoxicosis was severe but the correlation was not statistically significant. Correlation was not demonstrated between the AM and PAMP levels in thyrotoxic patients. CONCLUSIONS Elevation of the plasma adrenomedullin and proadrenomedullin-N terminal 20-peptide levels raises the possibility of involvement of these vasodilatory peptides in the haemodynamic changes in thyrotoxicosis.