The role of von Willebrand factor (vWF) in hemostasis was investigated morphologically in normal pigs infused with an anti-vWF monocolonal antibody which prolonged the bleeding time to 7.5-8.5 minutes. Morphology of the hemostatic plugs (HPs) at one and two minutes was basically similar to that of the untreated normal pig. Some HPs were formed at the ends of the transected vessels and some were adhering to the surface of the bleeding time incision. At seven minutes after bleeding time incision was made when the incision was oozing, large HPs were found and the ends of the small arteries were not covered with the HPs. The volume of HPs was calculated by integrating the areas of serial sections showing the volume of HPs formed in the incision increased with time. These findings were similar to those observed in von Willebrand's disease pigs. PAP staining was performed in the cryostat sections to investigate the localization of the infused monoclonal antibody in the tissue including the bleeding time incision. The antibody was localized to the HPs composed of platelets, individual platelets attached to the surface of the incision, and endothelial cells of the vessel. These in vivo findings suggest that vWF in the platelets and endothelial cells as well as in plasma plays an important role in the localization of the HPs to the damaged vessel.