1. Endothelin-1 and -3 induced marked arterial and venous constrictions in the perfused mesenteric vasculature of the rat with endothelin-3 being at least 20 times less active than endothelin-1, on both arterial and venous sides of the vasculature. 2. Two ETB selective agonists, BQ-3020 and IRL 1620 (500 pmol), induced weak constrictions of the venous mesenteric vasculature and were inactive in the arterial side at doses up to 1000 pmol. 3. In mesenteric vasculatures precontracted with either methoxamine (arterial side) or the thromboxane A2-mimetic, U46619 (venous side), acetylcholine or bradykinin produced vasodilations of both arterial and venous vessels, whereas endothelin-3 induced vasodilations only on the arterial side. 4. A selective ETA receptor antagonist, BQ-123, blocked, in a concentration-dependent and reversible fashion, the vasoconstrictions induced by endothelin-1 on both sides of the mesenteric circulation (IC50; arterial side: 0.013 microM; venous side: 0.032 microM). 5. In contrast, the vasodilator responses induced by endothelin-3 on the arterial side of the precontracted mesenteric vasculature were not affected by BQ-123. 6. The present study illustrates the presence of ETA receptors which are responsible for vasoconstriction by endothelins in the arterial and venous mesenteric vasculatures. Furthermore, we suggest that the vasodilations induced by endothelin-3 in the arterial vasculature uniquely, are ETB receptor-mediated.