A number of studies have been done relating to vasospasm. Vasospasm within the microvasculature of a flap can be one of the causes of ischemia and nonviability. Endothelin-1 (ET-1), a 21-amino acid polypeptide isolated from vascular endothelium culture media, is reported to be one of the most potent vasoconstrictors known. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia influenced plasma ET-1 levels. After the ischemic insult, blood was drawn from the venous effluent of the flaps. Plasma ET-1 levels after 6 hours of ischemia were significantly increased compared with nonischemic controls; they were 29 pM, i.e., almost enough to induce vasoconstriction of arterioles. These results suggest that ET-1 is one of the factors responsible for partial necrbsis of the skin flap, which contributes to the genesis of the no-reflow phenomenon.