Heme oxygenase (HO)-1 is a cytoprotective protein and has recently been identified as a graft survival gene. However, there are little data currently available regarding the expression of HO-1 in human living-related liver transplantation. This is the first report that HO-1 expression is increased in small-for-size liver allografts. We performed biopsies of the graft liver and donor liver left in six patients at four time points during the procedure and studied HO-1 expression by reverse-transcriptase polymerase chain reaction and immunohistochemistry. HO-1 mRNA was expressed at a low level in steady-state liver tissue but was strongly expressed after perfusion of the graft liver. HO-1 expression increased in nonparenchymal cells in the human graft liver. The number of HO-1 positive cells increased threefold by the end of liver transplantation. This study suggests that ischemia-reperfusion injury and excessive shear stress secondary to portal hypertension might augment HO-1 expression in the graft liver.