The aim of this study has been to investigate the plasma endothelin-1 (ET-1) levels in adult patients with proven Addison's disease (AD). Plasma ET-1 levels were measured in 29 subjects (17 males and 12 females, aged between 20 and 54 years): 15 of them were patients with AD and 14 were sex- and age-matched normal subjects, used as a control group. All patients with AD have been studied under basal conditions and nine of them also after 2 weeks on oral corticosteroid therapy (individual cortisol dosage ranging from 25 to 37.5 mg/day and 0.1 mg/day 9 alpha-fluorohydrocortisone). Extracted plasma ET-1 was determined by a specific radioimmunoassay using rabbit endothelin antisera. Mean ET-1 values in the patients with AD were three times higher than in normal subjects (21.09 +/- 4.38 pg/ml vs 6.72 +/- 1.74 pg/ml; p < 0.0001). Plasma ET-1 levels assayed in the patients with AD after 2 weeks of corticosteroid therapy were significantly decreased (14.47 +/- 3.7 pg/ml vs 22.8 +/- 5.2 pg/ml; -37%; p < 0.001) compared to values in untreated patients. However, the plasma ET-1 values obtained following corticosteroid therapy were still significantly higher (p < 0.001) than those detected in the control subjects. These results clearly indicate that patients with untreated AD have increased circulating ET-1 levels that may be reduced by short-term corticosteroid therapy.