The physiologic and potential pharmacologic roles of atrial natriuretic factor in congestive heart failure have remained confusing. We have evaluated the hemodynamic responses to human atrial natriuretic factor [ANF (102‐126)] given as bolus intravenous doses of 2.0 or 4.5 µg/kg to 12 patients with congestive heart failure. Responses were monitored with pulmonary and systemic arterial catheters in place. By 30 minutes after 4.5 µg/kg ANF (n= 6), heart rate decreased from 97 ± 16 to 91 ± 15 beats/min, right atrial pressure from 14 ± 4 to 12 ± 3 mm Hg, and pulmonary capillary wedge pressure from 33 ± 3 to 23 ± 2 mm Hg (allp<0.05); responses persisted for 120 minutes. Mean arterial pressure, cardiac index, stroke volume index, and pulmonic and systemic vascular resistances did not change significantly. The 2.0 µg/kg ANF dose produced similar responses, but only heart rate and right atrial pressure decreased significantly. No clinically important side effects were noted. High‐dose ANF bolus doses can be administered simply and safely and improve hemodynamic parameters in chronic heart failure. Therefore ANF does have pharmacologic activity in heart failure and may have therapeutic potential.Clinical Pharmacology and Therapeutics(1991)50,557–563; doi:10.103