The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.