From urine of orally hydrated normal persons a fraction was prepared by dialysis and ultrafiltration. This fraction, injected in normal and sodium depleted fasted rats, produced a dose-dependent increase in renal sodium excretion without change in renal potassium elimination. Glomerular filtration rate, renal plasma flow, and blood pressure are not affected by this urine fraction. Thus, the increase of natriuresis is the consequence of a diminished tubular sodium reabsorption, caused by the urine fraction applied. These results are interpreted as an evidence for a humoral natriuretic factor present in normal man after moderate oral hydration. Since urine preparations from patients with congestive heart failure fail to produce natriuresis in rats, it is concluded that insufficiency of this factor could be an explanation for the increased tubular sodium reabsorption and the development of edema in cardiac disease.