Platelet adhesion to human subendothelium was determined by perfusions with albumin solutions containing 51Cr-labeled, aspirin-treated platelets and washed red cells (hematocrit 40%) at 37° and a flow rate of 135 ml/min. Adherence was similar with Von Willebrand plasma instead of albumin solution and addition of purified FVIII-VWF caused adhesion similar to that from normal plasma. Incubation of subendotheliurn with FVIII-VWF resulted of binding of FVIII-VWF at the surface and in subsequent perfusions a surface concentration of, FVII-VWF/cm2 was shown to correct the platelet adhesion in albumin solutions towards normal. The kinetics of binding of FVIII-VWF and platelets to the subendothelium confirm the role of bound FVIII-VWF in adhesion. Binding of FVII-VWF occurs rapidly in the first minute of perfusion to about 4 x 10-4U/cm2 and then increases further to about 10-3 u/cm2 in 5 min. Platelet adhesion is similar for perfusates with and without FVIII-WF in the first minute; then the presence of FVIII-VWF results in a two-fold increase of adhesion at 5 min. Reduced adhesion was found with the high-molecular weight component of FVIII-VWF obtained by high iconic strength dissociation. Also, the activity of glycin precipitated FVIII-VWF (e.g. Hemofil FVIII-concentrate) is impaired, cross-electrophoresis of FVIII-VWF from cryoprecipitate and FVIII-VWF after glycin precipitation showed an increased mobility or the latter, indicating a reduced molecular siie. From these experiments we conclude tnat platelet adhesion is mediated by subendothelium-bound FVIII-WWF. The degree of adhesion may depend on the molecular weight of the FVIII-VWF.