Background. Human liver allografts sometimes show self-induced permanent tolerance without immunosuppression. It has recently been proposed that the replacement of liver donor endothelial cells by recipient cells could confer a survival advantage. The aim of this study was to analyze liver endothelial cell replacement in relation to the response (tolerance or rejection) after withdrawal of immunosuppression in liver transplant patients. Methods. Nine liver recipient patients were entered into a program of immunosuppressive drug withdrawal. The authors studied liver endothelial cell chimerism in five of these patients who received a liver from a donor of the opposite sex by in situ hybridization for X and Y chromosomes. Results. Three patients (33%) achieved complete withdrawal of immunosuppression. The authors' data show similar endothelial cell chimerism in both the tolerant and nontolerant patients analyzed. Conclusions. Endothelial cell chimerism has nothing to do with the induction of clinical tolerance in liver transplant patients after withdrawal of immunosuppression.