The pathogenesis of autoimmune liver diseases is poorly understood. Animal models are necessary to investigate antigen presentation and priming of T‐cells in the context of autoimmunity in the liver. Transgenic mouse models were generated in which the model antigen ovalbumin is expressed in hepatocytes (TF‐OVA) or cholangiocytes (ASBT‐OVA). Transgenic OT‐I (CD8) or OT‐II (CD4) T‐cells specific for ovalbumin were adoptively transferred into TF‐OVA and ASBT‐OVA mice to induce in vivo priming of antigen‐specific T‐cells. T‐cell migration and activation, as well as induction of liver inflammation, were studied. OT‐I T‐cells preferentially located to the liver of both mouse strains whereas no migration of OT‐II T‐cells to the liver was observed. OT‐I T‐cells proliferated in the liver of TF‐OVA mice and the liver and liver draining lymph nodes of ASBT‐OVA mice. OT‐II CD4 T‐cells were activated in spleen and liver draining lymph node of TF‐OVA mice but not in ASBT‐OVA mice. Transfer of OT‐I T‐cells led to histologically distinct inflammatory conditions in the liver of ASBT‐OVA and TF‐OVA mice and caused liver injury as determined by the elevation of serum alanine aminotransferase. Conclusion: An antigen expressed in hepatocytes is presented to CD8 and CD4 T‐cells, whereas the same antigen expressed in cholangiocytes is presented to CD8 but not CD4 T‐cells. In both models, activation of CD8 T‐cells occurs within the liver and causes liver inflammation. The models presented here are valuable to investigate the priming of T‐cells in the liver and their role in the development of autoimmune disease of the liver. (HEPATOLOGY 2007.)