Acute hemodynamic and humoral effects of synthesized alpha human atrial natriuretic polypeptide (alpha-hANP, 0.025 microgram/kg/min for 40 min) on 6 patients with severe congestive heart failure were assessed. Plasma alpha-hANP concentration was high in patients and increased further (from 463 +/- 360 to 1,282 +/- 670 pg/ml, mean +/- SD, p less than 0.01) following alpha-hANP infusion, but plasma norepinephrine (1,030 +/- 865 to 971 +/- 785 pg/ml) was not changed. Increases in urine output (1.0 +/- 0.8 to 2.6 +/- 2.3 ml/min) and Na+ excretion rate (87 +/- 89 to 257 +/- 211 mEq/min/m2) were statistically insignificant. A significant reduction was induced in mean aortic pressure (99 +/- 25 to 96 +/- 26 mmHg, p less than 0.05), mean right atrial pressure (11 +/- 9 to 7 +/- 8 mmHg, p less than 0.01), mean pulmonary arterial pressure (39 +/- 13 to 33 +/- 12 mmHg, p less than 0.05) and mean pulmonary capillary wedge pressure (27 +/- 8 to 20 +/- 7 mmHg, p less than 0.01). Heart rate, cardiac index, systemic vascular resistance and pulmonary vascular resistance were not altered. In conclusion, alpha-hANP induced decreases in left ventricular filling pressure and rightside heart pressure which were attributed to venodilatation rather than natriuresis in patients with congestive heart failure. Preserved cardiac output with decreased preload suggested that alpha-hANP improved cardiac function.