Human F8 transgenic mice develop antibodies against human fVIII when treated with a PEGylated human FVIII designated mFVIII2. Mice were treated with 8 weekly doses of either native human fVIII or 1 of 2 PEGylated human FVIII proteins (mFVIII1 and mFVIII2). Anti–human fVIII antibody titers against native human fVIII were determined by ELISA 1 week after the last dose. The asterisk denotes a statistically significant difference at the level P < .001. ns indicates not significant.