The virulence mechanisms of Moraxella catarrhalis that are involved in producing pulmonary infection are unknown. A well-characterized murine model was used to study the pulmonary clearance of M. catarrhalis and analyze the histopathologic changes and the role of phagocytic cells in the infected lungs. Ten strains of M. catarrhalis from various isolation sites were evaluated for their ability to resist pulmonary clearance. The rates of clearance of these strains, based on the percentage of the original inoculum remaining at 6 h after challenge, varied considerably. Histopathologic examination of lungs infected with 2 strains that exhibited very different clearance rates revealed similar pathologic responses. Analysis of the phagocytic cell response to these 2 strains revealed significant alveolar recruitment of granulocytes at 3, 6, and 24 h after bacterial challenge. However, granulocyte recruitment in response to strain B22, which was cleared readily, was significantly greater than to strain 035E, which resisted pulmonary clearance. This model system should facilitate investigation of the molecular basis of the interaction between M. catarrhalis and the lower respiratory tract.