Many factors influence renal sodium excretion and blood pressure. We tested the independent effects of dietary calcium (Ca; 500 mg twice daily), potassium (KCl; 20 mEq three times daily), sodium-potassium dependent ATPase inhibition (digoxin), calcium channel blockade (nifedipine), and placebo, on acute natriuresis in 14 normal subjects while receiving 150 mEq/d sodium diets and 2 L normal saline intravenously over four hours. Each subject received each regimen in random sequence. Sodium balance before infusion was not different among the regimens. Plasma renin activity (PRA) was increased in subjects receiving nifedipine, while the plasma aldosterone concentration (PA) was not different among the regimens. None of the regimens influenced the clearance of inulin or paraaminohippurate (PAH) either before or after saline infusion. Only KCl and nifedipine affected sodium excretion compared to controls. KCl and nifedipine increased the amount of sodium excreted after the infusion was terminated. In the case of nifedipine, this natriuresis was sufficient to increase the 24-hour sodium excretion on that day to above that of the other regimens. The data support the notion that potassium and nifedipine may decrease blood pressure by facilitating sodium excretion. Nifedipine may also uncouple renin from aldosterone. Oral calcium supplementation and sodium-potassium dependent ATPase inhibition did not facilitate natriuresis.