We developed an animal model of Legionnaires' pneumonia to permit study of aerosol infection, pathogenesis, and pulmonary host defense mechanisms in this disease. Guinea pigs and rats were exposed in a nose-only inhalation facility for 30 min to an aerosol of Burlington serogroup 1 Legionella pneumophila. Lungs contained 10(3) to 10(4) L. pneumophila immediately after exposure. Both guinea pigs and rats developed pneumonia, with 100% infectivity by microbiologic, histologic, and serologic criteria. Guinea pigs demonstrated illness, fever, and 56% mortality; rats showed little illness and 11% mortality. In both species, diffuse patchy pneumonitis coalesced and consolidated as the disease progressed. Aerosol challenge with 3H-L. pneumophila showed exponential growth of the bacteria in the lungs of both species. Guinea pigs and rats can be infected by aerosol exposure to L. pneumophila to produce a disease that closely simulates human Legionnaires' pneumonia. Rapid initial intrapulmonary growth suggests that resident lung defense mechanisms are quite ineffective against L. pneumophila, and that recruited or immunospecific defenses may be more critical in the outcome of infection. The difference in severity of illness between guinea pigs and rats may be exploited for different experimental designs.