Endothelial cells were cultured from the thoracic aorta, inferior vena cava, and pulmonary artery of normal adult and young pigs as well as from pigs with von Willebrand disease (vWD). The von Willebrand factor (vWF) was estimated by ELISA in endothelial cell supernatants and lysates as well as by immunofluorescence of cells by use of either a polyclonal or a monoclonal antibody to vWF. In normal adult pigs, the content of vWF in supernatants and cell lysates was the highest in the pulmonary artery, lower in the inferior vena cava, and almost nil in the thoracic aorta. In the normal young pigs, vWF was higher in the inferior vena cava endothelial cell supernatants and lysates than in the pulmonary artery. Thus the synthesis of vWF by endothelial cells varies along the vascular tree and appears to be modulated by the age of the animals. In pigs with vWD, levels of vWF were slightly detectable in endothelial cells from the pulmonary artery (contrasting with levels of plasmatic vWF below 0.01 U/ml), but were undetectable in the thoracic aorta and inferior vena cava. Thus, if vWF plays a role in atherogenesis, this involves circulating, not its intracellular, form.