The intracellular activity of three antimicrobial agents, erythromycin, clarithromycin, and ciprofloxacin, against Legionella pneumophila was examined in the human monocyte-derived cell line, THP-1, and the human alveolar epithelial cell line, A549. L. pneumophila multiplied by three- to four-log in THP-1 and by two- to three-log in A549 after 48-h incubation. The activity of the two macrolides was markedly greater in A549 than in THP-1, while ciprofloxacin exhibited similar activity in both cell lines. The intracellular concentrations of the two macrolides were markedly higher in A549 than in THP-1, while those of ciprofloxacin were almost equal in both types of cell lines. The intracellular activity of antimicrobial agents and the intracellular growth of L. pneumophila vary with different types of host cells.