Renal prostaglandins play a role in the control of renin release during chronic sodium depletion, during the acute phase of renovascular hypertension and in experimental low output heart failure in conscious dogs. However, with marked inhibition of the renin-angiotensin system, the adrenergic nervous system and the renal prostaglandins, PRA was still 17 times normal during chronic sodium depletion. After blockade of the adrenergic nervous system and the renal prostaglandins, PRA was 10 times normal during the acute phase of one-kidney renovascular hypertension. These findings demonstrate that other important mechanisms, possibly both the renal vascular receptor (so-called baroreceptor) and the macula densa, were involved. Both PGI2 and PGD2 given intrarenally increased renin release in both filtering and nonfiltering kidneys, but PGI2 was more potent than PGD2. Available evidence favors a role of PGI2 and it seems likely that the site of action is on the JG cells. Indomethacin produced a profound drop in CCr and CPAH during sodium depletion and in experimental heart failure which demonstrates an important role for the renal prostaglandins in the control of renal arteriolar tone. An important incidental finding is that renal denervation combined with propranolol administration decreased PRA from very high levels to normal in 50% of the dogs with experimental low output heart failure and a concurrent striking natriuresis occurred.