The effect of PGI2, the principal metabolite of arachidonic acid in mammalian arterial and venous tissues, on renal function and renin secretion was investigated in anesthetized, hypophysectomized dogs undergoing a maximal water diuresis. PGI2 in a concentration of 0.04 µg/kg/min significantly increased urine flow and urinary sodium and potassium excretion in the absence of changes in glomerular filtration rate or blood pressure. The fact that PGI2 significantly increased free water clearance and distal delivery of sodium and inhibited distal fractional reabsorption of glomerular filtrate is suggestive of an effect on proximal as well as distal sites of the nephron. PGI2 increased renin secretion rates threefold. This promotion of renin release may have been caused by an increase of ion flux across the macula densa or by an increase in renal blood flow. On a molar basis, PGI2 is about 10 times more potent than PGE2 with regard to natriuresis, diuresis and renin release when studied under identical conditions. Thus, PGI2 may be the major prostaglandin involved in the regulation of salt and water excretion