Blood was withdrawn at a constant rate from the cannulated carotid artery of an anaesthetized rat and perfused an ex vivo segment of tail artery cannulated at both ends and contained in an organ bath. Blood returned to the rat via a cannulated jugular vein. The tail artery was constricted and perfusion pressure increased by peri-arterial stimulation at 5 Hz for 5 s every 2 min. intravenous frusemide (5 mg/kg) decreased the stimulation responses of the tail artery. Diuresis-induced volume losses after frusemide were circumvented by a urinary bladder-intravenous shunt. Frusemide-induced reduction of tail artery vasoconstrictor responses was not seen in nephrectomized rats nor in rats pretreated with indomethacin or saralasin. indomethacin did not change responses already reduced by frusemide. Exogenous arachidonate or angiotensin II infused into the blood perfusing the tail artery did not alter stimulation responses. We conclude that intravenous frusemide administration to a rat reduces sympathetic vasoconstrictor responses of the ex vivo blood perfused tail artery segment by a diuresis-independent but prostaglandin and angiotensin II dependent release of another hormone from the kidney.