I'welve Aeromonas hydrophila isolates isolated from diseased fish in kafr El-Shiekh province were studied for their virulence in Nile Tilapia (Oreochromis niloticus). The most virulent five isolates used in this study shared a common resistance to the killing effect of Tilapia fish serum. Other factors such as lack of autoagglutiuation in 0.2% acriflavine, instability after boiling, production of an S-layer, proteases and haemolysins did not correlate well with virulence. In addition, serotyping could not group all the virulent isolates. On the other hand, serum resistance proved to be a good indicator for screening virulence of Aeromonas hydrophila isolates.