The effect of prostacyclin (PGI2), the major metabolite of arachidonic acid in arterial and venous tissue, on renal function was studied in hypophysectomized dogs under conditions of a maximum water diuresis. PGI2 (0.04 microgram/kg/min) significantly increased urine flow and urinary sodium and potassium excretion without affecting glomerular filtration rate. In addition, PGI2 significantly increased free water clearance and distal delivery of sodium and inhibited distal fractional reabsorption of glomerular filtrate. This suggests an effect of PGI2 on proximal as well as distal segments of the nephron. PGI2 is about 10 times more potent than PGE2 with regard to natriuresis and diuresis when studied under identical conditions. Thus, PGI2 may be the major prostaglandin involved in salt and water excretion.