It appears that the binding of coagulation factor VIII to von Willebrand factor in plasma stabilizes the otherwise highly labile factor VIII. A mathematical model of factor VIII kinetics has been developed based upon this proposed effect of factor VIII binding. The model’s kinetic parameter values have been estimated by fitting the model to data available in the medical literature. The model gives accurate quantitative predictions of the elevated steady-state concentrations of factor VIII in clinical conditions associated with the acute phase reaction and in pregnancy, the decreased steady-state concentrations of factor VIII in females heterozygous for hemophilia, the decreased steady-state concentrations of factor VIII in patients with type 1 (heterozygous) and type 3 (homozygous) von Willebrand disease, and the variable half-life of factor VIII in factor replacement therapy for hemophilia and von Willebrand disease.