Transgenic mice of subline E develop antibodies against human FVIII when treated with a modified human FVIII with high immunogenic potential. Transgenic mice (huF8) and conventional hemophilic E17 F8-knockout mice (E17F8 ko) were treated with 8 doses of either native human FVIII (FVIII) or 1 of 2 PEGylated human FVIII proteins (mFVIII1 and mFVIII2). Titers of antibodies against native human FVIII were determined by ELISA 1 week after the eighth dose. Results for individual mice are shown. ns indicates that the difference was not significant. *P < .001.