Currently, prostacyclin, endothelin receptor antagonists and phosphodiesterase inhibitors are recommended therapy in idiopathic pulmonary arterial hypertension. However, each of these drugs has limited efficacy in the improvement of clinical symptoms, pulmonary hemodynamics and long-term survival. Levosimendan, a novel calcium-sensitizing inodilator agent, has been shown to have pulmonary vasodilatory action. However, the potential pulmonary vasodilating effect of levosimendan in patients with idiopathic pulmonary arterial hypertension remains unclear. Levosimendan administered in two patients with nonvasoreactive idiopathic pulmonary arterial hypertension exhibited deterioration in clinical status, and, contrary to what was expected, levosimendan was found to increase pulmonary pressures and did not lead to a substantial improvement of the patient's condition. J Cardiovasc Med 10:503-507 (C) 2009 Italian Federation of Cardiology.