Background-Vessel dilator, a 37-amino acid peptide hormone synthesized in the heart, enhances urine flow 4-to 12-fold and sodium excretion 3-to 6-fold in healthy humans. The present investigation was designed to determine whether vessel dilator might have similar beneficial effects in persons with congestive heart failure (CHF). Methods and Results-Vessel dilator (100 ng/kg body weight per minute) given intravenously for 60 minutes to NYHA class III CHF subjects increased urine flow 2-to 13-fold, which was still increased (PϽ0.001) 3 hours after its infusion was stopped. Vessel dilator enhanced sodium excretion 3-to 4-fold in CHF subjects (PϽ0.01), which was still significantly (PϽ0.01) elevated 3 hours after infusion. Vessel dilator decreased systemic vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary wedge pressure 33%, and central venous pressure 27% while increasing cardiac output 34%, cardiac index 35%, and stroke volume index 24% without significantly affecting heart rate or pulmonary artery pressure in the CHF subjects. The control CHF patients did not have any changes in the above parameters. Conclusions-These results indicate that vessel dilator has significant beneficial diuretic, natriuretic, and hemodynamic properties in humans with congestive heart failure. (Circulation. 1998;98:323-329.)