We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11±0.9 fmol/ml in NL and 71±9.9 in CHF (P < 0.01); the latter with twofold night ventricular increment (P < 0.05). In NL, ANF infusion of 0.10 ig/ kg per min (40 pmol/kg per min) induced increases (P < 0.05) of absolute (from 160±23 to 725±198 iseq/min) and fractional(1-4%) sodium excretion, urine flow rate (from 10±1.6 to 20±2.6 ml/min), osmolar (from 3.2±0.6 to 6.8±1.2 ml/min) and free water (from 6.8±1.6 to 13.6±1.6 ml/min) clearances, and filtration fraction (from 20±1 to 26±2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P < 0.01). Systolic blood pressure fell (from 112±3 to 104±5 mmHg, P < 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11±1 to 7±1 mmHg, P < 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P < 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P < 0.05) but not in CHF.