The role of prostaglandin I2 (PGI2) in the renal vasodilatation induced by acetylcholine (ACh) was examined in indomethacin (Indo)treated dogs receiving an infusion of PGI2. Renal arterial infusion of ACh (40mug/min) in control dogs produced an increase in sodium excretion and renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or renin secretory rate (RSR). In dogs pretreated with indomethacin (Indo), an inhibitor of prostaglandin synthesis, renal arterial infusion of ACh produced an increase and then a decline in sodium excretion accompanied by a progressive fall in GFR and RPF and a progressive rise in RSR. Renal arterial infusion of PGI2 (0.2mug/min) before and during the infusion of ACh restored the natriuretic and vasodilatory response to ACh in Indo-treated dogs. The data suggest that Indo shortens the natriuretic and vasodilatory response to ACh by inhibiting synthesis of prostaglandins, possibly PGI2, and that PGI2 may play a role in the renal vasodilatory effect of ACh.