Hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) is characterized by vascular hemorrhage and acute renal failure. Angiopoietin-1 (Ang-1) is a glycoprotein that maintains vessel integrity and reduces endothelial permeability. We found that in HTNV-infected human umbilical vein endothelial cells (HUVECs) the levels of Ang-1 mRNA and protein were reduced on days 2 and 3 post-infection (p.i.), when endothelial permeability was increased. The HTNV-stimulated permeability was reduced by treatment of HUVECs with Ang-1. The plasma Ang-1 level was lower in HFRS patients than in healthy persons. Paired plasma samples of HFRS patients revealed markedly lower Ang-1 levels during the acute phase of HFRS as compared to the convalescent phase. These findings suggested that HTNV reduced the Ang-1 expression in endothelial cells that might play an important role in the increase of vascular permeability in HFRS.