Plasma half-life and organ uptake of endothelin 1 (ET-1) was studied in anaesthetized Wistar rats administering a bolus of 125I-labeled ET-1 into jugular vein, with and without a preceding dose of 1-80 ng of unlabeled ET-1, via the same route. Plasma half-life of intact 125I-ET-1 was 40 sec and that of total radioactivity 68 sec. Immunoreactivity of circulating 125I-ET was rapidly reduced, by 23% at 30 sec and by 43% at 360 sec, respectively. High power liquid chromatography of plasma extracts revealed a corresponding decrease of intact 125I-ET-1 peak with time. There was a predominant uptake of 125I-ET-1 in the lungs, 82%, and lesser by kidneys, 10%, heart 3.6%, liver, 2.7%, and spleen, 1.5%, respectively. Pretreatment with unlabeled ET-1 caused a dose-dependent shift of uptake from lungs to kidneys. We conclude that circulating ET-1 is rapidly cleared, primarily by the lungs, which may play an important role in protecting the systemic circulation from the vasoconstricting actions of ET-1.