Ghrelin is a novel GH-releasing peptide that may also induce vasodilation and a positive energy balance through GH-independent mechanisms. However, the hemodynamic, renal, and hormonal effects of ghrelin in patients with chronic heart failure (CHF) remain unknown. Accordingly, 12 patients with CHF were given an iv infusion of human ghrelin (0.1 microg/kg.min) or placebo. Ghrelin significantly decreased mean arterial pressure (-9 mm Hg, P < 0.05) without a significant change in heart rate. Ghrelin significantly increased cardiac index (+25%, P < 0.05) and stroke volume index (+30%, P < 0.05), although it did not significantly alter mean pulmonary arterial pressure or pulmonary capillary wedge pressure. Infusion of ghrelin induced a marked increase in serum GH level (15-fold), associated with slight increases in circulating epinephrine, ACTH, cortisol, and PRL. Infusion of ghrelin did not significantly alter urine volume, urinary sodium excretion, or creatinine clearance. These hemodynamic, renal and hormonal parameters remained unchanged during placebo infusion. In summary, iv infusion of ghrelin, a potent GH-releasing peptide, had beneficial hemodynamic effects in patients with CHF in the absence of renal effects.