A dose-defined aerosol infection of pigs was used to study the immunogenic and protective potentials of oral immunization with dead or live Actinobacillus pleuropneumoniae serotype 9 reference strain CVI 13261 against an aerogenic challenge. Pigs were vaccinated with a single dose of 10(11) CFU of viable (n = 8) or inactivated (n = 8) A. pleuropneumoniae given orally in a gelatin capsule. After 3 weeks, vaccinated pigs and nonvaccinated controls were challenged aerogenically with a dose of 10(8) CFU of A. pleuropneumoniae CVI 13261. The protective efficacy of oral immunization was evaluated by clinical and postmortem examinations. Bronchoalveolar lavage in pigs was performed during the experiment to obtain lavage samples for assessment of local antibodies. Isotype-specific antibody responses in sera and in bronchoalveolar lavage fluids were determined by enzyme-linked immunosorbent assays based on whole-cell antigen. Oral immunization did not induce clinical side effects. After aerosol challenge, two animals of both vaccinated groups (25% in each case) showed a moderate fever for 2 days, whereas all four pigs (100%) of the nonvaccinated control group developed severe fever. In contrast to the controls, which developed severe pleuropneumonia, the vaccinated pigs had only mild pulmonary lesions. Three weeks after challenge, 13 of 16 vaccinated pigs (81%) were found to be free of pathomorphological changes of the lungs. From two of these pigs immunized with live bacteria we were able to reisolate A. pleuropneumoniae. A significant systemic and pulmonary increase in the concentrations of immunoglobulin A (IgA), IgM, and IgG antibodies reactive with A. pleuropneumoniae was detectable after aerosol challenge in both vaccinated groups. Immunization with viable bacteria was found to induce significantly higher concentrations of each Ig isotype in bronchoalveolar lavage fluids and sera than immunization with inactivated A. pleuropneumoniae. These serological findings were not reflected in the reduction in clinical disease after challenge in comparison to the case for the pigs vaccinated with inactivated bacteria. We concluded that a single oral administration of A. pleuropneumoniae provides partial clinical protection against aerosol challenge infection in the respiratory tract.