It has recently been demonstrated that the rate of both hydrogen and potassium excretion can be acutely increased when a disproportion is created between the quantity of sodium and the quantity of penetrating anion available for reabsorption (1). This experimental condition was achieved by the infusion of neutral sodium phosphate into animals which had previously been maintained on a diet poor in sodium chloride. Such short-term observations raised the possibility that sustained changes in availability of penetrating anion might of themselves induce chronic alterations in body fluid composition. This hypothesis was supported by the subsequent observation that restriction of dietary chloride prevents correction of plasma bicarbonate elevations induced by chronic hypercapnia or administration of desoxycorticosterone acetate (DOCA) (2, 3). In each of the latter circumstances, however, the elevated plasma bicarbonate presumably developed as a result of direct acceleration of sodium-cation exchange and these observations, therefore, throw no light on the possible consequences of a primary loss of chloride in a normal animal. Such a loss might be expected to produce either secondary sodium (and volume) depletion, diversion of sodium reabsorption to the cation-exchange mechanism, or some combination of the two. In order to investigate this problem, chloride deficiency has been produced in dogs by the repeated infusion of nitrate, an anion known to induce chloruresis (4).