The pathophysiological basis of idiopathic edema is not yet fully understood. To elucidate further the mechanism by which this syndrome occurs, natriuretic factor (NF) has been measured in the urine of 10 female patients with idiopathic edema receiving a diet containing 3-4 g NaCl a day. Twenty-four hour urines collected on an ambulatory basis were fractionated through a G-25 Sephadex column and fraction IV, which has been previously shown to possess natriuretic activity, was tested on a rat assay. Five of these patients exhibited NF activity averaging 183.2 +/- 68.7%, which was in agreement with their salt intake. In contrast, the remaining 5 patients have very high NF activity (1462.6 +/- 273.2%) on the same diet. An additional patient studied for 9 days under metabolic conditions and receiving 120 mEq NaCl a day retained the sodium ingested and gained 5.1 kg body weight. The NF activity increased from 367 to 2616% over the 9 day observation period, although no diuresis occurred at any time. In conclusion, 50% of the patients with idiopathic edema exhibited peripheral resistance to the action of the NF, a fact which may explain the syndrome. It may further serve to differentiate patients with "true idiopathic edema" from those with diuretics abuse.