We have shown that bovine HMW kininogen remarkably accelerates the activation of Factor XII and prekallikrein in the presence of kaolin, adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region (Sugo et al., 1980; Ikari et al., 1981). The present study was undertaken to examine the role of HMW kininogen in the activation of Factor XII and prekallikrein with other negatively-charged surfaces. The activation system used here was as follows; (1) Activation of prekallikrein by Factor XII, (2) Activation of Factor XII by plasma kallikrein and (3) Activation of prekallikrein by Factor XIIa. Among a variety of foreign surfaces, amylose sulfate and sulfatide were the most efficient in the activation reaction of Factor XII and prekallikrein. Bovene HMW kininogen accelerated all the three reactions triggered by these surfaces. However, the accelerating effect of HMW kininogen on the activation of Factor XII by plasma kallikrein was very weak, when amylose sulfate or sulfatide was used as surface. The three reactions were highly dependent on the amounts of HMW kininogen and surfaces contained in the reaction mixtures. Excess amount of them inhibited these reactions. Among the various fragments, which were prepared from HMW kininogen digests with plasma and urinary kallikreins (Sugo et al., 1980), a large fragment consisting of fragment 1.2 and light chain accelerated the reactions. Thus both fragment 1.2 and the light chain region in HMW kininogen were essential for these activation reactions.