Technical Abstract: Bacteriophage are viruses that infect and kill bacteria. Bacteriophage do not infect animal and plant cells making them a potentially safe alternative to antibiotics. We have conducted research on the efficacy of bacteriophage to both prevent and treat colibacillosis in poultry. Bacteriophage lytic to a non-motile, serotype O2 isolate of Escherichia coli were isolated from municipal waste water treatment plants and poultry processing plants. This E. coli isolate is pathogenic to poultry, causing a severe respiratory and systemic infection. Two bacteriophage isolates were selected to use in studies designed to determine the efficacy of these bacteriophage to prevent and treat severe colibacillosis in poultry. Colibacillosis was induced by injecting 6 X 10**4 cfu of E. coli into the thoracic airsac when the birds were 1 week of age. Initial studies demonstrated that mortality was significantly reduced when the challenge culture was mixed with bacteriophage prior to challenging the birds. In subsequent studies, we have shown that an aerosol spray of bacteriophage given to the birds prior to this E. coli challenge can prevent the disease, and that an intramuscular injection of bacteriophage provides an effective treatment of this disease. We have demonstrated that bacteriophage can be used to both prevent and treat colibacillosis in poultry and may provide an effective alternative to antibiotic use in animal and human medicine.