It has recently been shown that epithelial cells derived from stem cells originating outside the liver are integrated into liver allografts. Whether epithelial intragraft chimerism protects transplants from rejection or chronic transplant dysfunction, and whether it interferes with recurrence of primary liver disease, is not known. Twenty-seven sequential biopsies derived from 9 liver-transplant recipients were studied for chimerism of hepatocytes and cholangiocytes. The target cells were isolated by laser microdissection after cytokeratin immunolabeling and genotyped using DNA analysis of a highly polymorphic short tandem repeat. Irrespective of whether early (up to 4 weeks) or late (more than 12 months) posttransplantation biopsies were studied, cholangiocyte chimerism was almost constantly found in 91% of the samples. No significant differences occurred between samples derived from patients with chronic organ dysfunction (n = 3), recurrent hepatitis (n = 3), or mild, unspecific changes (n = 3). By contrast, hepatocyte chimerism tended to occur later (55% vs. 22%) and appeared to be associated with recurrent hepatitis (67% vs. 27%). In this respect, chronic organ dysfunction did not differ from mild, unspecific changes. While cholangiocyte chimerism represents a constant and early phenomenon in liver transplantations, an enhanced chimeric integration of recipient-derived hepatocytes can be observed in recurrent hepatitis, supporting the concept of an increased recruitment of extrahepatic progenitor cells to the liver in chronic hepatitis.