Actinobacillus pleuropneumoniae causes a common, acute respiratory disease of pigs seen worldwide. Vaccination and antimicrobials are used to control the disease but are inadequate and the disease remains a major problem in intensively grown pigs. Signature-tagged mutagenesis was used to identify mutants of A. pleuropneumoniae which had reduced virulence. A number of mutants were incapable of causing experimental disease. The hypothesis was formed that a non-pathogenic mutant could occupy the niche or site of carriage of A. pleuropneumoniae and hence reduce or eliminate carriage and susceptibility of the pig to disease. One mutant (4074-14D5) was selected with the aim of deliberate infection and colonisation of the respiratory tract in order to (a) competitively exclude virulent A. pleuropneumoniae and (b) displace existing A. pleuropneumoniae from its niche in the crypts of the palatine tonsil lymphoid tissue. Results showed the avirulent mutant to be capable of persisting in the palatine tonsil and the nasal secretion for at least 14 days. Animals pre-colonised with 14D5 and then challenged with wild-type A. pleuropneumoniae were still susceptible to colonisation by wild- type A. pleuropneumoniae. Animals pre-colonised with wild-type A. pleuropneumoniae remained colonised in the face of high-dose inoculation with the avirulent mutant. In conclusion, use of an avirulent mutant of A. pleuropneumoniae did not exclude or prevent wild-type infection and it could not displace established colonisation by the wild-type pathogen.