A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.