Blockade of prostaglandin synthesis with indomethacin (1) did not induce significant changes in blood pressure or in renal circulation in renovascular hypertensive rabbits with normal renal blood flow; (2) induced renal insufficiency and aggravated hypertension in hypertensive rabbits whose renal blood flow was below normal levels; (3) did not alter the reversal of renovascular hypertension produced by the release of the renal arterial constriction; and (4) induced a decrease in plasma renin activity by decreasing renin release. These findings indicate that the vasodilator and natriuretic actions of prostaglandins may play an important role in protecting the kidney against ischemia; the facilitating role of renal prostaglandins on renin release raises the possibility that a primary hypersecretion of renal prostaglandins is responsible for Bartter's syndrome, whereas a primary deficiency may be responsible for "low-renin hypertension."