Chronic rejection is an important cause of liver allograft failures. The allograft undergoing chronic rejection shows affected large- and medium-sized muscular arteries with homing of foamy macrophages and enlargement of the intimal area. The objective of this study was to elucidate the pathogenesis of the intimal lesion that causes obliterative arteriopathy by identifying the origin of the foamy macrophages and mesenchymal cells present in the intimal area. Nine allografted livers (6 male and 3 female patients) from sex-mismatched donors undergoing chronic rejection were studied by combined staining of the macrophages or the mesenchymal cells in the intimal area with immunohistochemistry and in situ hybridization using a probe for the human Y chromosome. By using the specimens from female donor allografts transplanted to male recipients, it was found that 62 +/- 11% of CD68+ foamy macrophages and 71 +/- 4% of smooth muscle actin-positive mesenchymal cells in the intimal lesions and a few interstitial myofibroblasts were positive for the Y chromosome probe. This indicated that they were derived from the recipients. In conclusion, the thickening intimal lesion seen in obliterative vasculopathy in liver allografts consists of the foamy macrophages and mesenchymal cells of recipient origin. These circulating recipient cells migrated to the areas in advance of remodeling arteries.