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The effect of 16α-hydroxyprogesterone on sodium, chloride and potassium balance was studied in four »normal« human subjects and one patient with hypopituitary adrenocortical insufficiency on a metabolic ward. Each subject was maintained on a constant intake of sodium, chloride, and potassium, and the daily 24-hour urinary excretion of these electrolytes and creatinine was measured, together with serial determinations of the corresponding serum concentrations. In three of the »normal« subjects, the administration of 16α-hydroxyprogesterone induced a saluresis, unaccompanied by a significant change in the potassium balance or endogenous creatinine clearance. A similar effect was observed in the patient with adrenocortical insufficiency, who was treated concomitantly with large dosages of deoxycorticosterone. One apparently »normal« subject, whose glomerular filtration rate was abnormally low, failed to respond to the administration of the steroid. These results indicate that 16α-hydroxyprogesterone is capable of exerting a natriuretic and chloruretic effect, similar to that observed with spironolactone and certain other endogenous adrenal steroids.