The immunogenicity of platelets that contain FVIII in FVIII^null mice with preexisting anti-FVIII immunity. FVIII^null mice were immunized with rhF8 (50 U/kg per week × 4) to induce anti-FVIII antibody development. The 2bF8^Tg platelets were infused into rhF8-primed mice. The transgenic platelets were transfused to a level between 21% and 41% of total platelets upon infusion. (A) Schematic diagram of platelet infusion in FVIII^null mice with preexisting anti-FVIII immunity. (B) Anti-FVIII inhibitor titers in rhF8-primed FVIII^null mice after transfusion of 2bF8^Tg platelets. (C) Anti-FVIII total IgG titers in rhF8-primed FVIII^null mice after transfusion of 2bF8^Tg platelets. (D) Anti-FVIII inhibitor titers in rhF8-primed FVIII^null mice after rechallenge with full dose of rhF8 (50 U/kg per week × 4). (E) Anti-FVIII inhibitor titers in rhF8-primed FVIII^null mice after rechallenge with low dose of rhF8 (2 U/kg per week × 4). These results show that transfusion of platelets containing FVIII does not trigger an anti-FVIII memory response in FVIII-primed FVIII^null mice. *P < .05.