Plasma concentrations of endothelin-1 (ET-1) were measured in 25 hyperthyroid subjects, 15 hypothyroid subjects, and 21 age-matched normal controls. In hyperthyroid patients, plasma concentrations of ET-1 were significantly higher than in the control group (P < .0001) and in hypothyroid patients (P < .0001). In contrast, no differences were found between hypothyroid patients and controls. Plasma levels of ET-1 were similarly elevated as in patients with Graves' disease and those with toxic adenoma. No correlations were found between plasma ET-1 levels, thyroid hormones, and thyrotropin (TSH) in hyperthyroid, hypothyroid, and euthyroid groups. The results of our study clearly indicate that in hyperthyroidism, circulating levels of ET-1 are strongly increased, although the pathogenesis of the increase is unclear.