A NEW concept of regulation of sodium excretion by the mammalian kidney has evolved since the work of DeWardener et al.1,2. During extracellular fluid volume expansion, a factor or factors other than changes in glomerular nitration rate and mineralocorticoid hormone activity influence sodium diuresis. The same factor(s) appear to contribute to the natriuresis per nephron initiated by nephron reduction and observed in advancing renal disease3. In both extracellular fluid volume expansion and nephron reduction there is evidence4,5 that a humoral substance inhibits sodium reabsorption in single proximal tubules of rats. At least a part of the natriuretic activity may be humorally mediated4 and Rector et al.5,6 have termed the active agent the "natriuretic hormone". The agent has also been called the "third factor" (glomerular filtration rate representing the first factor and mineralocorticoid hormone activity the second factor).