Abstract: Although eosinophil infiltrate has been recognized in hepatic graft-versus-host disease, its significance in relation to hepatic graft-versus-host disease lesions is unknown. In the present study, we analyzed hepatic eosinophil infiltration in relation to bile duct damage in experimental mouse graft-versus-host disease across minor histocompatibility barriers up to 14 months after transplantation. Portal eosinophil infiltration was found from 1 week after transplantation throughout the entire 14-month observation period. It was most striking during the early chronic stage of hepatic graft-versus-host disease between 2 to 7 months, with a peak at 5 months after transplantation. Microscopic and electron microscopic study revealed eosinophils infiltrated around the bile duct as well as in the bile duct epithelial layer. They were commonly found together with lymphocytes but were also occasionally found singly around the bile duct and in the bile duct epithelial layer. Bile duct epithelial cells in contact with and in the vicinity of eosinophils showed a variety of degenerative changes, occasionally associated with the presence of extracellular eosinophil granules. Bile duct epithelial cells with eosinophil infiltration just beneath the basement membrane frequently showed further characteristic severe degenerative changes with shedding or dropping-off into the lumen, which features were quite similar to those seen in the bronchial epithelium in asthma patients. These results indicate that not only lymphocytes but also eosinophils may be involved in the production of the bile duct injury in hepatic graft-versus-host disease, especially in its early chronic stage.