A total of 138 E. coli isolates obtained from fecal samples of various mammals and birds and water samples of different origin were compared. The comparison included multiple antibiotic resistance to a total of 21 antibiotics, the protein profile (PAGE) of the isolates, the DNA fragments of each isolate after treatment with the restriction enzymes, HindIII, EcoRI, EcoRV, BamHI and BglII and the presence of plasmid(s). Our results indicated that human, horse and Nile water isolates were resistant to 62% of the antibiotics used, while cat isolates were resistant to 47%, mouse isolates 72%, avian to 34%, Ismailia canal 67%, household water reservoir 81% and swimming pool isolates were resistant to 57%. Protein profile (PAGE) analysis is the second method used; the protein with 20.29 kd molecular weight is common in avian, household water reservoir and swimming pool isolates. The third method includes DNA fragments using different restriction enzymes HindIII, EcoRI, EcoRV, BamHI and BglII.