1. The technique of chloride titration was employed in twenty dogs to determine the pattern of renal chloride handling in response to systematic increases in filtered chloride load. The influence of variations in sodium reabsorption on this pattern was also assessed by producing a wide spectrum of volume expansion during the titration protocols. 2. The results indicate that chloride reabsorption is proportional both to the rate of chloride filtration and to the rate of sodium reabsorption and, hence, that the specific pattern of each chloride titration curve is the fortuitous consequence of the interplay between these two factors. 3. The rate of chloride reabsorption relative to the simultaneous rate of sodium reabsorption was used as an index of the ability of the kidney to maintain chloride homeostasis and indicated that the kidney invariably tends to return depressed. plasma chloride concentration towards normal but, under the conditions of these acute experiments, consistently tends to reduce elevated plasma chloride concentration only when cation reabsorption is markedly depressed. 4. The present observations do not elucidate the mechanism responsible for these findings but suggest that plasma chloride concentration is not regulated through the operation of a threshold mechanism.

1. The interrelationship between extracellular fluid volume and extracellular anion composition as determinants of sodium excretion was studied in thirty-four dogs. In six, hypovolaemia, hypochloraemia and hyperbicarbonataemia were induced by the administration of ethacrynic acid and a low chloride diet. Isotonic sodium bicarbonate was then infused resulting in a progressive increase in sodium excretion. After 3 h while continuing the sodium bicarbonate infusion, an infusion of hydrochloric acid was given in order to return extracellular anion composition towards normal. This resulted in a prompt fall in sodium excretion without a change in GFR. 2. Ten studies were performed to determine whether this hydrochloric acid-induced enhancement of sodium conservation depends upon the presence of volume depletion and sodium avidity or whether it could also be demonstrated under circumstances of volume expansion. In these studies, hypervolaemia, hypochloraemia, hyperbicarbonataemia and a brisk natriuresis were induced by infusing isotonic sodium bicarbonate into normal dogs. The addition of hydrochloric acid returned anion composition to normal and, as before, resulted in a prompt suppression of sodium excretion despite continued sodium loading and enhanced glomerular filtration. 3. Results obtained from three related protocols (six animals each) confirmed that hypochloraemia and hyperbicarbonataemia were the necessary prerequisite conditions for this effect of hydrochloric acid in volume expanded animals. We interpret these findings as evidence that the response of the kidney to changes in extracellular fluid volume may be significantly affected by changes in the extracellular concentration of physiologic anions.