The impact of VWF on functional plasma FVIII:C levels in various mouse models of VWD. We compared how VWF impacts plasma FVIII:C expression levels in VWF^2N/−, VWF^2N/+, VWF^2N/2N, VWF^+/+ (littermates), VWF^+/−, and VWF^−/− mice. We crossed VWF^2N/2N with VWF^−/− mice to generate compound heterozygous VWF^2N/- mice. Blood samples were collected from mice via retro-orbital venous plexus bleeds using 3.8% sodium citrate as an anticoagulant. Plasma VWF:Ag levels were determined by ELISA using anti-mVWF specific antibodies, and pooled plasma from wild-type C57BL/6J mice was used as the standard. Plasma FVIII:C levels were determined by a chromogenic assay, and rhF8 was used as the standard. (A) Plasma VWF:Ag levels. (B) Plasma FVIII:C levels. *P < .05; **P < .01; ***P < .001; ****P < .0001. n.s., no statistically significant difference between the 2 groups. These data demonstrate that the viability of plasma FVIII:C in VWD model mice is governed by its association with or inability to associate with VWF.