Warfarin prevents the initiation of an immune response to FVIII. FVIII−/−/BALB/c mice were pretreated with warfarin (n = 6) or PBS (n = 7) before the first and third of 5 intraperitoneal injections of 1 μg FVIII. This experiment was repeated twice, and representative data are shown. Seven days after the last injection, (A) serum samples were analyzed for antibody response (582 ± 232 [FVIII] vs 101 ± 24 μg/mL [FVIII + warfarin]; *P = .042) and (B) splenic T cells from the mice treated with FVIII or FVIII + warfarin were assayed for the response to FVIII (**P = .002). These data indicate that other coagulation factors besides FVIII are probably necessary for initiation of the immune response.