Legionella appear to be a new group of organisms which can be classified as intracellular pathogens. Evidence from our laboratory and others indicates that killed vaccines and serum can protect guinea pigs against intraperitoneal (i.p.) infection. We have developed an aerosol model of infection. Using this model, we have shown that various vaccination regimens using acetone- or heat-killed cells protect against i.p. but not aerosol challenge at comparable LD50 doses. Lack of protection against aerosolized organisms occurs in spite of serum antibody. In this grant we propose to try a variety of vaccination procedures to find ones which will give protection against inhaled Legionella, and to investigate the importance of serum antibody, antibody in lung lavage fluid, and of cell-mediated mechanisms in host defenses to aerosol challenge as compared with i.p. challenge. Further, the ability of several vaccines to confer cross-protection against different serogroups and species of Legionella will be tested. These studies can be expected to increase our knowledge concerning the mechanisms of immunity to Legionella on both the practical and theoretical levels, and should also increase our understanding of host defense mechanisms in the lung.