Hemophilia A is a common disorder of blood coagulation caused bydeficiency of factor VIII. The disorder is inherited as an X linked recessivetrait . Abnormalities in factor VIII gene include deletions, insertions, pointmutations and inversion. Factor VIII gene inversions are rare defects in thehemophilias, except for an inversion involving intron 22 of the factor VIIIgene. The aim of this study was to investigate of intron 22 restrictionfragment length polymorphism (RFLP) by PCR using XbaI restrictionenzyme in hemophilic patients, this may help to determine patients who aremore likely to have intron 22 inversion, to screen FVIII gene for othermolecular abnormalities as deletions and point mutations by multiplex PCR ,and to screen FVIII for a point mutation in exon 25 by using BsrDIrestriction enzyme.Our research revealed the following molecular abnormalities in thestudied hemophilia A patients: factor VIII gene RFLP in intron 22 by usingXbaI restriction enzyme: 30% XbaI (+), 67.5% XbaI (-ve), 2.5% intron 22deletion, partial F. VIII gene deletion in 10% of cases and exon 25 pointmutation in 7.5% of cases. We concluded that the study of intron 22polymorphism by XbaI restriction enzyme may be used to select thehemophilia A patients who have a severe disorder and are negative for theXbaI polymorphic marker, or who have intron 22 deletion to be investigatedfor factor VIII gene intron 22 inversion. In addition the spectrum of genedefects in Egyptian haemophiliacs was found as heterogeneous as reportedin other populations, and that multiplex PCR followed by agarose gelelectrophoresis offers a simple and sensitive way for mutation screeningwhich is essential for carrier detection and prenatal diagnosis of this fataldisorder.