1. We have attempted to confirm the existence of a natriuretic hormone released in response to acute expansion of blood volume.
2. Isolated kidneys, perfused with whole blood at constant pressure, were incorporated within an extracorporeal circulation in recipient rats. In six control experiments urine flow rate, renal blood flow, glomerular filtration rate, filtration fraction, and the fractional excretion of filtered sodium and water were measured for periods of up to 120–140 min thereafter. The same variables were measured in a further 12 experiments in which, after 63 ± 11 min, the rats were volume expanded with equilibrated whole blood (15, 18 or 28 ml/kg body wt.).
3. On average the controls revealed no change in any of the variables measured; volume expansion was followed by increased renal blood flow and fractional excretion of filtered sodium and water, while the filtration fraction fell.
4. In both the control and volume-expansion experiments, there were 12 instances in which the fractional excretion of filtered sodium increased; in 10 of these, including those experiments in which the natriuresis was most marked, there was a closely correlated fall in filtration fraction.
5. In all the experiments changes in the fractional excretion of filtered sodium and water varied in parallel.
6. We conclude that volume expansion (a) changes the concentration of some circulating vasoactive substance(s) and (b) results in natriuresis and diuresis consequent upon a fall in filtration fraction.