Equilibrium distribution of water, sodium, and potassium was studied in rats given Pitressin tannate or aldosterone for 2 weeks in the absence of both adrenal and neurohypophysis. Pitressin shifts water from environment into cells (gastrocnemius, aorta) and produces a loss of sodium from both compartments such that both [Na]o and [Na]i decrease. This is accompanied by a rise in [K]o and a fall in [K]i, in large part explicable in terms of the water shift. Aldosterone shifts water from cells to environment and induces a gain in sodium in both compartments such that both [Na]o and [Na]i increase. This is accompanied by a fall in [K]o and a tendency to a rise in [K]i, in large part ex-plicable in terms of the water shift. Pitressin and aldosterone thus produce basically opposite effects on the transcellular distribution of salt and water. The adrenal-deficient state depends negatively on the absence of adrenal function and positively on unopposed but not necessarily excessive neurohypophyseal function. In contrast, diabetes insipidus requires positive unopposed adrenal function and hence, not surprisingly, is inhibited by chlorothiazide.