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Abstract The present study was planned to: 1) Isolate a pathogenic strain of A. hydrophila from naturally diseased 0. niloticus and then evaluate the pathogenicity of the isolated strain through experimental infection to apparently healthy 0. niloticus. 2) Isolate and select antagonistic Bacillus species from the gastrointestinal tract of apparently healthy 0. niloticus based on in-vitro antagonistic test against A. hydrophila. And then test the safety of the isolated antagonistic Bacillus species to apparently healthy 0. niloticus. 3) Evaluate the effect of the dietary application of antagonistic Bacillus species (1.0 X 107 cfu/g diet) on the immune response and resistance of 0. niloticus to A. hydrophila infection after two feeding periods (15 and 30 days). Also the viability of the Bacillus species in the prepared feed was examined weekly after storage at refrigerator and at room temperature for up to 6 weeks. The results can be summarized as follows: A pathogenic strain of A. hydrophila was isolated from naturally diseased 0. niloticus showed signs of haemorrhagic septicemia. The pathogenicity of the isolated strain revealed that intra- peritoneal inoculation of A. hydrophila (0.5 X 108 cfu/fish) into apparently healthy 0. niloticus induced 90% mortality among the inoculated fish. The observed signs and P IM findings on the experimentally infected fish were similar to that recorded on naturally diseased fish, including darkening skin, signs of hemorrhagic septicemia, hyperemia and hemorrhage at different parts of the body, scales losses, skin erosions, fin rot and abdominal distension (ascites |