Bacteriophages are viruses that can infect and kill bacteria. Three studies were conducted to determine the efficacy of bacteriophage to prevent an Escherichia coli respiratory infection in broiler chickens. In the first study 3-d-old-birds were challenged with an air sac inoculation of 10(3) cfu of E. coli per mL mixed with either 10(3) or 10(6) pfu of bacteriophage, or 10(4) cfu E. coli mixed with 10(4) or 10(8) pfu of bacteriophage. In the second study, drinking water of birds to 1 wk of age was treated with 10(3) or 10(4) pfu of bacteriophage per mL and birds were air sac challenged with 10(3) cfu of E. coli, or water was treated with 10(4) or 10(6) pfu of bacteriophage per milliliter and birds were challenged with 10(4) cfu of E. coli. In the third study, birds were air sac challenged at 1 wk of age with 10(4) cfu of E. coli and given 10(5) or 10(6) pfu of bacteriophage per mL of water from 1 d of age to 2 wk of age. In Studies 1 and 2, there were two replicate pens per treatment with 10 birds per pen, and in Study 3, there were four replicate pens per treatment with 10 birds per pen. The studies were all concluded when the birds were 3 wk of age. In Study 1, BW was decreased at 1 and 2 wk of age in the birds that were challenged with 10(3) or 10(4) cfu of E. coli and was decreased at 2 wk of age in the birds challenged with 10(4) cfu of E. coli mixed with 10(4) pfu of the bacteriophage. Mortality was decreased from 80% in the birds challenged with 10(3) cfu of E. coli to 25 and 5% when mixed with 10(3) or 10(6) pfu of the bacteriophage, respectively. Mortality was decreased from 85% in birds challenged with 10(4) cfu of E. coli to 35% when mixed with 10(4) pfu of the bacteriophage, and no mortality occurred when mixed with 10(8) pfu of bacteriophage. There was essentially no protection observed in Studies 2 and 3 when the birds were challenged with 10(3) or 10(4) cfu of E. coli with bacteriophage present in their drinking water at any level. These data suggest that bacteriophage can protect birds from a respiratory challenge with E. coli, but that adding the bacteriophage to the drinking water offered no protection to the birds. The complete protection of the birds observed in Study 1 suggests that bacteriophage may possibly be developed as an alternative to antibiotic use in poultry.