In advanced heart failure, severe edema develops associated with hyponatremia. In 20 patients with severe congestive heart failure, we studied plasma antidiuretic hormone (ADH) concentrations related to hemodynamics and plasma osmolality. Prazosin was used to test the acute response to changes in atrial receptors and hemofiltration to test the response to changes in volume receptors. One group of the patients had inappropriately high ADH values (14.5 +/- 8.8 pg/ml) in relation to their plasma osmolality, which was well below normal values (276 +/- 23 mosmol/kg water) with no apparent osmoregulatory control. The other group showed a normal relationship of ADH and plasma osmolality (3.9 +/- 1.0 pg/ml; 289 +/- 8 mosmol/kg water), Only in the normal regulating group did lowering of left atrium pressure by prazosin result in a rise in ADH related to the decrease in pressure. Inappropriately high ADH secretion could be reversed by hemofiltration. This suggests that the syndrome of "dilutional hypo-osmolality" in severe congestive heart failure may be caused by an inappropriately high ADH secretion in which the osmoreceptor system is dominated by nonosmolar stimuli; however, it cannot be ruled out that associated hemodynamic effects in the kidney or other intrarenal or hormonal factors contribute to this mechanism.