nomically important diseases in modern pig production worldwide. The Enterisol®Ileitis vaccine havebeen shown to reduce clinical disease and to increase weight gain, however, while the natural infectionwith L. intracellularis can provide complete protection against re-infection, this has not been achievedby this vaccine. We therefore undertook a detailed characterization of immune responses to L. intracel-lularis infection in vaccinated pigs (VAC) compared to previously infected pigs (RE) in order to pinpointimmunological determinants of protection.Results: The VAC pigs shed L. intracellularis to the same extent as non-vaccinated pigs after challenge,however less L. intracellularis in ileum and lymph nodes was seen post mortem. In the RE group, challengedid not lead to L. intracellularis shedding and no challenge bacteria were found post mortem. In both VACand RE the acute phase haptoglobin response was diminished and L. intracellularis specific IgG responseswere delayed and reduced compared to non-vaccinated pigs. On the other hand L. intracellularis specificIFN- responses tended to develop faster in the VAC group compared to controls.Conclusion: Although vaccinated and non-vaccinated pigs shed L. intracellularis at similar levels afterchallenge, a lower number of intestinal L. intracellularis was observed in the vaccinated pigs at postmortem inspection. This might be due to the observed faster CMI responses upon challenge in vaccinatedpigs. Complete protection against infection without L. intracellularis shedding, however, was only seenafter a previous infection resulting in IFN- production predominantly by CD8+and CD4+CD8+cells.Improved protective vaccines against L. intracellularis should therefore target stimulation of these T cellsubsets.