Virulent strains of Legionella pneumophila that are preincubated with specific antiserum are cytotoxic for alveolar macrophages when added at a multiplicity of infection of 100 L. pneumophila per macrophage. Under the same conditions, avirulent strains exhibit little cytotoxic activity. Virulent strains are also resistant to the bactericidal activity of normal human serum and fail to bind complement components on the cell surface. In contrast, avirulent strains are serum-sensitive and both C3 and C9 are deposited on the surface. Results of experiments suggest that the shift from virulence to avirulence of L. pneumophila may be the result of the selection of a small number of avirulent cells present in the population of a virulent culture.