The effect of endothelin on the release of prostacyclin was examined in perfused rat mesenteric arteries with or without their pretreatment with indomethacin. Porcine endothelin at 10 pmol (a subpressor dose) and 40 pmol stimulated the release of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin. Rat endothelin also stimulated its release, but less than porcine endothelin. Pretreatment with indomethacin completely inhibited this 6-keto-PGF1 alpha release. These results indicate that endothelin stimulates the release of prostacyclin from mesenteric arteries. This release may modulate the action of endothelin locally.