Von Willebrand factor (vWf) is an adhesive glycoprotein known to play an important role in hemostasis and in tissue injury. Because the latter process resembles hepatic fibrogenesis, we studied the tissue distribution of vWf in diseased livers. In normal rat liver vWf was strongly expressed in the vascular endothelium and as small spots or fiber-like structures in the hepatic parenchyma. During acute liver injury, pronounced staining was observed within the area of necrosis. In fibrotic livers vWf deposits were distributed predominantly at the scar-parenchyma interface but also within the septum and in sinusoidal lining cells. Testing different liver cell populations in vitro demonstrated that vWf gene expression was limited to endothelial cells (ECs) and, therefore, the latter cell population might represent the vWf-positive cells detected in vivo. The distribution of vWf within fibrotic septa suggests that vWf becomes a component of the extracellular matrix (ECM) in fibrotic livers.