With this acute respiratory infection model, we demonstrated in vivo efficacy of phage BcepIL02 in decreasing bacterial density and lung inflammation during infection. These positive treatment effects were not observed with either UV-inactivated phage or l phage, and BcepIL02 was ineffective against infection with B. cenocepacia K56-2, a strain resistant to BcepIL02. These findings indicate that active and specific phages are required for effective treatment.