The M2 protein of influenza A virus is expressed on the surfaces of infected cells, and a monoclonal antibody to this protein inhibits plaque enlargement of sensitive influenza A viruses without reducing plaque titer (S.L. Zebedee and R.A. Lamb, J. Virol. 62:2762-2772, 1988). In the current study, passively transferred monoclonal antibody to M2 reduced the level of replication of influenza A virus but not of influenza B virus in the lungs of mice. These experiments demonstrated that antibody to a protein conserved among influenza A virus subtypes inhibits virus growth in vivo.