Recent observations suggest that plasma F VIII consists of a series of molecules with different molecular weights. The data described in this paper suggest that sup F VIII represents the molecules with relatively low molecular weights whereas the molecules with the highest molecular weights appear in cryo F VIII. Sup F VIII was associated with VIII:C and VIIIR:Ag, but ristocetin cofactor activity was lacking. Although the immunoprecipitation characteristics of sup F VIII with rabbit antifactor VIII were different from those of cryo F VIII, immunological identity was observed in immunodiffusion and crossed immunoelectrophoresis. In 0.8M NaCl sup F VIII dissociated into VIIIR:Ag of relatively high molecular weight and VIII:C of low molecular weight. No indications were obtained that the presence of sup F VIII was the result of proteolytic degradation of factor VIII. VIII:C of sup F VIII was more labile in vitro than VIII:C in plasma. It could be activated by traces of thrombin in a way similar to plasma F VIII. In patients with classic von Willebrand's disease relatively more VIII:C remained in the supernatant after cryoprecipitation of plasma.