The immune response in FVIII^null mice that were preconditioned with a nonmyeloablative regimen followed by an early phase of platelet-FVIII or low-dose rhF8 transfusion. FVIII^null mice were preconditioned with 660-cGy TBI. Twenty-four hours later, animals were infused with 2bF8^Tg platelets or low-dose rhF8 (2 U/kg) weekly for a total of 8 infusions and subsequently challenged with full-dose rhF8 (50 U/kg per week × 4). (A) Schematic diagram of the transfusion in preconditioned FVIII^null mice. The transgenic platelets were transfused to a level between 17% and 85% of total platelets upon infusion in the first round and between 20% and 56% in the second round. (B) The titers of anti-FVIII inhibitors in animals that received 2bF8^Tg platelet transfusion. (C) The titers of total anti-FVIII IgG in animals that received 2bF8^Tg platelet transfusion. (D) The titers of anti-FVIII inhibitors in animals that received low-dose rhF8 infusion. (E) The titers of total anti-FVIII IgG in animals that received low-dose rhF8 infusion. These results demonstrate that transfusion of 2bF8^Tg platelets or low-dose rhF8 together with 660-cGy TBI preconditioning suppresses the anti-FVIII immune response in FVIII^null mice. LD, low dose.