The interrelationships between acetylcholine (ACH) and prostaglandins in the control of sodium excretion (U<sub>Na</sub>V) and of renin secretion (RS) were examined in unilaterally-nephrectomized, anesthetized dogs with or without treatment with indomethacin, an inhibitor of prostaglandin synthetase. Intrarenal infusion of ACH (40 µg/min) in control animals produced diuresis and natriuresis. U<sub>Na</sub>V was 9.2 ± 3.1 µEq/min during control periods and was 74.7 ± 31.6 µEq/min after 40 min of infusion of ACH (p < 0.05). U<sub>Na</sub>V was still 48.0 ± 16.8 µEq/min after 100 min of infusion of ACH (p < 0.05). RS rate was 930.6 ± 188.5 U/min during control periods, and was 737.4 ± 220.3 U/min after 100 min of infusion of ACH (p > 0.1). In the dogs treated with indomethacin, the natriuresis produced by ACH could not be sustained. U<sub>Na</sub>V was 46.6 ± 12.1 µEq/min before and was 34.7 ± 12.8 µEq/min 100 min following the infusion of ACH (p >0.1). Arterial plasma renin activity was 3.29 ± 0.83 ng/ml/h before and was 20.97 ± 7.78 ng/ml/h after 100 min of infusion of ACH (p < 0.025). The data suggest that prostaglandins are involved in the sodium excretion and the renin secretion produced by acetylcholine.