Bacteriophages are viruses that kill bacteria. They are plentiful in nature with no known activity in human or animal cells, making them an attractive alternative to antibiotics. The objective of this research was to determine if a coarse or a fine spray of bacteriophage would prevent colibacillosis induced by an intratracheal (IT) challenge with Escherichia coli. Two studies were conducted with 6 treatments: untreated control, birds treated with a spray administration of bacteriophage and not challenged, birds administered bacteriophage IT and not challenged, birds not treated and challenged IT with E. coli, birds sprayed with bacteriophage and IT challenged with E. coli, and birds administered bacteriophage IT and challenged IT with E. coli. There were 3 replicate pens of 10 birds per pen, per treatment, and all treatments were administered at 1 d of age. Study 1 was concluded when the birds were 19 d of age, and study 2 was concluded when the birds were 21 d of age. In both studies, neither a coarse nor a fine spray protected the birds from an IT E. coli challenge; however, when bacteriophage was administered IT there was complete protection. This research demonstrates the necessity for the administration of bacteriophage therapeutics to deliver high bacteriophage titers to the site of a bacterial infection.