Primary and secondary immunoglobulin class-specific antibody responses in serum and pulmonary lavage fluids of mice were studied after respiratory infection and intramuscular vaccination with influenza virus. Infection and vaccination with inactivated virus vaccine induced primary IgM and IgG antibody responses in the serum and pulmonary lavage fluids (PLF). Neither immunizing method induced detectable serum IgA antibodies, and only infection generated IgA antibodies in PLF. The major portion of antibodies in PLF was derived from serum, but local synthesis of IgG and IgA antibodies was detected after virus infection. Vaccination of infection-primed mice boosted the IgM and IgG antibody concentrations in serum and PLF but had no effect on IgA antibody concentrations. Nonlethal infection of vaccine-primed mice generated secondary IgM and IgG antibody responses in serum and PLF and an IgA antibody response in PLF. Again, most of the antibody detected in PLF was derived from serum, but low concentrations of IgA and IgG were synthesized locally after infection. Although mice immunized with inactivated vaccine lacked the capacity to synthesize IgA antibody, they were protected from severe pulmonary disease when challenged with lethal influenza virus. These data support the concept that serum IgG antibodies are sufficient for prevention of severe pulmonary disease.