The aim of this study was to investigate liver histology in mice after immunization with the conserved self molecule dihydrolipoamide dehydrogenase, E3, a subunit of the mitochondrial 2-OADC enzyme family identified as the M2 autoantigen in the liver disease, primary biliary cirrhosis. Mice were immunized by a novel procedure. The autoantigen E3 was introduced by pinocytosis into hypertonically treated syngeneic lymphoid cells to facilitate intracellular antigen processing and presentation and the generation of a cytolytic T cell response. Liver sections were examined and scored for evidence of an inflammatory response by two independent procedures: standard microscopy with visual scoring, and automated scanning with computerized scoring. There was a close correlation between read-outs of liver histology by standard microscopy and automated scanning, using the index of mononuclear cellular infiltrations in hepatic portal tracts. Such infiltrates were prominent in the immunized mice, but, unexpectedly, the degree of infiltration was similar in mice injected with autoantigen (E3)-loaded syngeneic cells, or syngeneic cells treated only with hypertonic medium. The equivalent changes in the liver with the experimental and control protocol is indicative of the reactivity of the liver to any provocative immune stimulus, and is cautionary for protocols designed for the induction of autoimmune liver disease in experimental animals.