Experiments were carried out to determine the infectivity, clinical course of disease, and lethality of aerosols of Legionella pneumophila for guinea pigs. The median infectious dose was 5 organisms. In addition, the intraperitoneal 50% lethal dose was 3.0 × 106 cells, a value indicating that the organisms were less virulent by the intraperitoneal route than by aerosol. Nonfatal disease always included fever and weight loss. These signs were accompanied by sporadic bacteremia and dyspnea. Leukocyte counts were uninformative. In general, the severity of fever and extent of serologic (microagglutination titer) response were dose-related. The guinea pig may be used as a model for Legionnaires' disease, but the only dependable clinical criteria of infection after airborne challenge are weight loss, fever, and seroconversion.