Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, produced strong contractions in human cerebral, meningeal and temporal arteries. The isopeptides ET-2 and ET-3 also showed potent constrictor activity; however, ET-3 was less potent. The selective ETA receptor antagonist FR 139317 mediated a shift to the right of the concentration-response curve of ET-1. These results suggest that the powerful constriction elicited by the endothelin-isopeptides in cerebral, meningeal and temporal arteries is mediated through ETA receptors.