Relaxin is upregulated and plays a compensatory role in human heart failure. We therefore determined the safety of and dose response to human relaxin in stable patients with heart failure. Sixteen patients were treated with open-label intravenous relaxin in three sequential dose cohorts and monitored hemodynamically during the 24-h infusion and postinfusion periods. The safety demonstrated in group A (treatment for 8 h each with dosages equivalent to 10, 30, and 100 μg/kg/day) allowed escalation to group B (240, 480, and 960 μg/kg/day), and the highest safe dose, 960 μg/kg/day, was selected for a 24-h dosing in group C. Relaxin showed no relevant adverse effects and produced hemodynamic effects consistent with systemic vasodilation, i.e., trends toward increases in the cardiac index and decreases in pulmonary wedge pressure, without inducing hypotension. The first therapeutic use of relaxin in human heart failure demonstrated favorable hemodynamic effects and indicated that it may be of value in the treatment of this widespread disease.