We studied the effect of a stable, cyclic ether analogue of prostaglandin endoperoxide (EPA) on canine renal function, hemodynamics, and renin release. Infusion of EPA into one renal artery decreased renal blood flow in a dose dependent manner. At a dose of 10(-7) g/kg/min the renal blood flow decreased from a baseline of 384 to 267 ml/min/100 g. This flow decrease was unaltered by phentolamine and saralasin, but was potentiated by prior treatment with indomethacin. Urine flow, glomerular filtration rate, sodium, and potassium excretion all decreased in a dose dependent manner; however, neigher fractional excretion of sodium nor free water clearance showed any significant change, making direct tubular effects of EPA unlikely. EPA caused a significant increase in renin release that was completely blocked by prior treatment with indomethacin. We conclude that EPA is a potent renal vasoconstrictor and that this vasoconstriction is responsible for the renal functional changes observed. Renin release is not a direct effect of EPA but probably is secondary to an endogenously generated prostaglandin. Since EPA mimics the effects of natural prostaglandin endoperoxides on smooth muscle in vitro, it is possible that prostaglandin endoperoxide-induced vasoconstriction in vivo modulates the effects of their vasodilatory products, prostaglandin E2 and I2.