Background Pulmonary arterial hypertension (PAH) is a poor prognostic disease with limited treatment options. Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle hypercontraction, so the purpose of this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in patients with PAH. Methods and Results Fasudil 30 mg was intravenously injected over 30 min in 8 patients (all female, mean±SD, 41±11 years) with PAH. The lowest total pulmonary resistance (TPR) time was within 30-60 min after administration. Administration of fasudil decreased TPR from 1,069±573 dyne· s· cm-5 to 809±416 dyne· s· cm-5 (p< 0.005) and mean pulmonary arterial pressure from 41.3±12.8 mmHg to 37.9±14.6 mmHg (p< 0.05). The cardiac index was increased from 2.42±0.73 L· min-1· m-2 to 2.84±0.79 L· min-1· m-2 (p< 0.02). Systemic vascular resistance and systolic systemic arterial pressure (SAP) were decreased (p< 0.005, p= 0.09, respectively), but the decrease in SAP was small (-6.4±9.1 mmHg). Conclusion These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.(Circ J 2006; 70: 174-178)