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An animal model of the clearance of nontypable Haemophilus influenzae has been developed to determine both optimal immunization strategies for controlling colonization of the respiratory tract in patients with damaged airways and mechanisms of action of immune clearance. It was demonstrated that stimulation of gut-associated lymphoid tissue (GALT) (either by direct injection or by ingestion of antigen) followed by local administration of antigen into the bronchus was required to enhance clearance in this model. The primary effect of GALT immunization persisted for at least 6 wk; it was specific and could not be replaced by systemic immunization. Failure to stimulate locally in the bronchus was associated with protracted clearance. No clear correlation between local or systemic antibody and bacterial clearance was demonstrated; however, immunized rats were shown to have faster recruitment of phagocytic cells to the bronchial spaces, and these phagocytes had a higher activity state than cells harvested from nonimmunized animals. It is probable that bacterial clearance is accelerated in immunized animals due in part to factors mediating a change in the behavior of luminal phagocytes.