Legionella anisa and the amoeba Hartmannella vermiformis were isolated from an indoor fountain implicated as the infectious reservoir in an outbreak of Pontiac fever. We evaluated the ability of this strain of L. anisa to multiply in cultures of an amoeba (H. vermiformis), a ciliated protozoan (Tetrahymena pyriformis), and human mononuclear cells and to infect guinea pigs. These bacteria multiplied in the culture of H. vermiformis but failed to infect guinea pigs or the cultures of T. pyriformis and human mononuclear cells. These findings suggest that some Legionella spp. may multiply only in specific protozoan hosts. The inability of this strain of L. anisa to multiply in human phagocytic cells may be related to the development of Pontiac fever rather than pneumonic legionellosis in exposed individuals. Further studies are necessary to determine whether the ability of legionellae to infect certain host cells can be correlated to differences in human disease.