The irreversibility of the contractile action of endothelin-1 (Et) and of its binding to its receptors are usually believed to be linked in a direct manner. Rat aortic strips were exposed to 25 nM Et for short periods of time that were sufficient to irreversibly saturate membrane receptor sites and then washed of unbound Et. Under these conditions, fast and transient contractile responses were observed. They were unlike the slow and irreversible contractions observed in the continued presence of the peptide. They were as fast as KCl, angiotensin II and vasopressin contractions. It is concluded that the irreversibility of Et contractions and of its interaction with its receptors can be uncoupled. The data also suggests that recycling of endocytosed Et receptors contributes to the sustained contractile action of the peptide.