Data presented herein and previously support an active role for platelets in promoting the interaction and activation of the coagulation proteins of the contact phase of intrinsic coagulation. The platelet membrane, activated by ADP collagen or thrombin, can promote the proteolytic activation of factor XII to factor XIIa in the presence of kallikrein and high molecular weight kininogen. The zymogen factor XI associates with high molecular weight kininogen in plasma and becomes bound to a site on the membrane of thrombin or collagen activated platelets. Thereafter, platelet bound factor XI can be proteolytically activated to factor XIa either in the presence of factor XIIa or in the presence of kallikrein. These observations could explain the absence of bleeding complications in patients with factor XII deficiency. In addition, platelets contain a molecule which has a higher molecular weight than plasma factor XI and possibly consists of a tetramer of four identical subunits of 52000 daltons each of which is functionally and immunologically similar to plasma factor XI. Since this molecule is present in the platelets of patients with severe plasma factor XI deficiency and no evidence of bleeding, we postulate that platelet factor XI can substitute for plasma factor XI in hemostasis and possibly account for the considerable variability in clinical severity observed in patients with factor XI deficiency.