The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.