To investigate a possible pathophysiological role of human adrenomedullin (AM), we measured the plasma concentration of immunoreactive-AM (ir-AM) in 38 patients with end-stage renal disease (ESRD) on hemodialysis (HD) and 38 healthy subjects (age and sex matched). In addition, plasma ir-AM was characterized by a reverse-phase high performance liquid chromatography. The mean value (+/- SEM) of plasma AM in the patients before HD (10.1 +/- 0.67 fmol/ml) was markedly higher than that in the control group (2.9 +/- 0.13 fmol/ml, p < 0.001), but plasma AM levels were not altered by HD. There was a significant correlation between plasma AM levels and mean blood pressure (MBP) in a group of subjects including both patients before HD and healthy subjects (p < 0.01). In chromatographic study, the major peak of ir-AM in the plasma from patients on HD, as well as healthy subjects, emerged at an elution time identical to that of synthetic AM, indicating that the active form of AM was present in the circulating blood. The secretion of AM seemed to be increased in response to the conditions elicited by ESRD such as hypervolemia and/or hypertension, and reduced renal excretion of the peptide may also contribute to its high plasma level.