Antibody levels in sera and respiratory secretions and resistance to respiratory infections were examined in mice given live infuenza virus in small-particle (2 mum) aerosols, large-particle (10 mum) aerosols, intraperitoneally, and subcutaneously. After parenteral administration antibody was found primarily in the serum, but small amounts were recovered in bronchoalveolar washings after 2 to 3 weeks. Specific antibody was present in both sera and bronchoalveolar washings from mice given virus in small-particle aerosols to achieve virus dissemination throughout the respiratory tract. Immunoglobulin A, immunoglobulin G, and trace amounts of immunoglobulin M, all specific for the infecting virus, were detected in bronchoalveolar washings of small-particle aerosol-infected mice. Virus administration in large-particle aerosols (for primary virus localization in upper respiratory tract) at doses greater than those required to initiate infection with small-particle aerosols failed to stimulate production of antibody in sera or bronchoalveolar washings. Small-particle aerosol-immunized mice were resistant to subsequent challenge with 10(2.0) respiratory median lethal doses of virulent virus, whereas large-particle aerosol-immunized mice were not protected. Parenteral immunization modified the course of the disease in challenged mice and reduce mortality rates but did not prevent reinfection of the respiratory tract.

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