The hemodynamic effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) were evaluated in a double-blind, placebo-controlled study with echocardiography and systolic time intervals in 11 healthy volunteers. During an infusion of alpha-hANP for 30 min, when plasma ANP concentration increased to a peak level of approximately 300 pg/ml, an increase occurred in diuresis (+174%, p less than 0.01 vs. placebo) and natriuresis (+148%, p less than 0.05). Heart rate increased (+10%, p less than 0.05), but the mean arterial pressure remained unchanged. The left ventricular end-diastolic diameter was reduced (-3%, p less than 0.01), as was the left ventricular end-systolic diameter (-11%, p less than 0.001). Total peripheral resistance (-12%, p less than 0.05) and midsystolic circumferential wall stress (-16%, p less than 0.05) decreased, while cardiac output increased (+15%, p less than 0.05), as did fractional shortening (+15%, p less than 0.001). Within 30 min postinfusion, all differences between the ANP and placebo treatments had disappeared. No significant difference between the treatments was observed in preejection period or preejection period/left ventricular ejection time ratio. In conclusion, when administered as a short infusion, alpha-hANP causes peripheral arterial vasodilation and thus, by reducing left ventricular afterload, improves the pump function of the heart. Venous vasodilating effect of alpha-hANP may contribute to the decrease in left ventricular preload, but a diuresis-induced reduction in circulating intravascular volume may also be influenced.