Pertussis is a respiratory disease caused by bacteria that grow only on the ciliated epithelium of the respiratory tract. We are currently studying the dissemination of a protective mucosal immune response from the gut associated lymphoid tissue to the respiratory tract in a mouse model of respiratory infection. Intraduodenal as well as intranasal immunization of adult mice with endotoxin-free filamentous hemagglutinin prior to aerosol challenge decreases the number of B. pertussis recovered from the lungs and tracheas in comparison to unimmunized infected animals. Antibodies to FHA can be detected in the lungs and serum of intraduodenally or intranasally immunized mice at the time of respiratory challenge. We have developed an in vitro assay designed to enumerate antigen specific memory B lymphocytes recovered from the respiratory mucosa following oral immunization. Using this assay, we have detected a significant increase in the number of FHA specific memory B lymphocytes in the lungs of mice following infection as well as after intranasal immunization. Current efforts are also directed toward the cloning of protective epitopes of B. pertussis antigens into bacterial vectors that will colonize the murine gut mucosa in order to evaluate the protective capacity of a live oral vaccine against B. pertussis.