Regional hemodynamic responses to bolus doses (4 and 40 pmol) and 60-min infusions (12 and 120 pmol/h) of endothelin-2 (ET-2) and sarafotoxin-S6b (S6b) were measured in conscious Long-Evans and Brattleboro rats chronically instrumented with pulsed Doppler flow probes. In both strains of rat the two bolus doses of ET-2 and S6b peptides caused an initial fall in mean blood pressure (MBP). At the higher dose S6b caused a greater fall in MBP than ET-2. In Long-Evans rats the fall in MBP after S6b was associated with renal, mesenteric, and hindquarters vasodilatations; in Brattleboro rats there was no renal or mesenteric vasodilatation with S6b. The high dose of ET-2 caused early mesenteric vasoconstriction in both strains. After the initial fall in MBP there were dose-dependent increases in MBP together with renal and mesenteric vasoconstrictions. These effects were generally greater after S6b than after ET-2 and no less marked in Brattleboro than in Long-Evans rats, indicating that release of endogenous vasopressin was not an indispensable component of the response. Infusions of the higher dose of ET-2 or S6b caused increases in MBP only, associated with renal, mesenteric, and hindquarters vasoconstrictions. The results indicate that S6b is a more potent stimulus than ET-2 of vasodilator mechanisms in vivo; despite this, S6b also exerts more marked vasoconstrictor effects than ET-2.