BACKGROUND AND OBJECTIVE A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure. DESIGN Plasma AM levels were measured in patients with proven Addison's disease using a specific radioimmunoassay and compared to those in healthy normotensive subjects. PATIENTS Eighteen patients with Addison's disease (10 men and eight women; ages 21 to 72 years) and 21 healthy control subjects (13 men and eight women; ages 20 to 71 years) were enrolled in the study. All patients were studied under basal conditions and 10 were reassessed following corticosteroid treatment. RESULTS All patients with Addison's disease showed increased levels of AM compared to the control group. Mean plasma AM levels were correspondingly higher in patients with Addison's disease than in normal subjects (102.1±33.4 (SD) ng/l versus 13.7±6.1 ng/l; P<0.0001). In 10 patients studied after corticosteroid treatment, plasma AM levels were significantly reduced (P<0.0001: 110.3± 35.8 ng/l versus 32.4±10.3 ng/l) after 2 weeks of treatment. A weak correlation (r=0.458; P=0.048) was observed between systolic blood pressure and plasma AM concentrations in all patients with Addison's disease. CONCLUSIONS These results indicate a consistent but reversible increase of adrenomedullin in patients with Addison's disease.