We compared the natriuretic and diuretic effect of an intravenous infusion of 1–28 human atrial natriuretic peptide (hANP) (0.1 µg/kg/min over 30 min) in 10 patients with congestive heart failure (CHF) and in 10 control subjects of similar age and sex. In the controls, urine volume rose from 36.8 ± 8.55 to 115.6 ± 34.2 ml/30 min and urinary sodium excretion from 4.55 ± 0.8 to 11.2 ± 2.24 mEq/30 min before and during the infusion of ANP, respectively. In patients, baseline urine volume and sodium output were similar, however, rise in urine volume and urinary sodium was greatly reduced during the infusion of hANP. In patients with CHF, baseline plasma ANP levels (604.1 ± 135.3 vs. 39.4 ± 5.85 pg/ml;p < 0.005) and urinary excretion of cyclic GMP(cGMP) (41.8 ± 5.22 vs. 15.2 ± 4.19 nmol/30 min; p < 0.05) were significantly elevated compared to controls. The absolute and relative rise in cGMP excretion, however, was blunted in patients with CHF. In the controls, angiotensin I-converting-enzyme (ACE) inhibition by enalapril significantly reduced the urinary output of sodium and water after ANP infusion. Plasma ANP levels and urinary cGMP remained unaltered by ACE inhibition. Furthermore, treatment with enalapril resulted in a rise in renin and a drop in aldosterone levels. The reduction of plasma renin and serum aldosterone by ANP was maintained after ACE inhibiton. In the patient group, administration of enalapril (3 × 2.5 mg every 6 h) reduced ACE activity in the serum from 84.7 ± 16.9 to 2.13 ± 0.88 U/l. Arterial blood pressure was lowered from 114.7 ± 6.69 to 106.1 ± 7.25 mm Hg systolic and from 76.9 ± 3 to 69.2 ± 3.7 mm Hg diastolic. However, natriuresis and diuresis and creatinine clearance following infusion of ANP remained unaltered.