Sodium (Na) depletion, due to uncompensated loss of parotid saliva, reduces the pressor responsiveness to angiotensin II (AII) in intact conscious sheep. 2. Inhibition of prostaglandin synthesis by indomethacin restored AII pressor responsiveness in Na-deplete sheep. 3. Indomethacin infusion also increased the pressor responsiveness to AII in the Na-replete sheep. 4. These findings suggest that in vivo prostaglandins may play a role in modulating the pressor responsiveness to angiotensin II in sheep.