Human endothelin, a 21-residue peptide produced by vascular endothelial cells, was infused intravenously into trained conscious dogs at a rate of 20 ng'kg^^min"¹ for 1 hr. Endothelin produced a renal vasoconstriction that persisted during a 40-minute recovery period. Sarafotoxin S6b, a closely related 21-residue peptide that has been isolated from the venom of the burrowing asp, was also infused into the same conscious dogs at 20 ng^kg'-^min"¹. Sarafotoxin produced a renal vasodilation that persisted throughout the infusion; when the infusion ended, however, renal blood flow decreased rapidly to below control levels. Both endothelin and sarafotoxin produced marked decreases in urine osmolality even though plasma vasopressin remained normal, thus indicating that these peptides inhibit the antidiuretic effects of vasopressin. These results imply that a broad spectrum of structure-activity relationships may exist among analogues of this unique group of 21-residue peptides.