The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). The glycoprotein hormone, thrombopoietin (TPO), is the major regulator of megakaryopoiesis and platelet production. 1,2 Northern blot analyses have demonstrated that TPO mRNA is expressed predominantly in liver, and to a minor degree, in kidney, spleen, and brain. 3,4 A recent report from this laboratory has shown that hepatic TPO mRNA accounts for 94% of the total in the perinatal period. 5 In situ hybridization studies have localized TPO mRNA in parenchymal cells of the human 6 and murine 7 liver. Hepatocytes appear to produce TPO at a constant rate. The plasma concentration of the hormone is regulated by the degree of receptor-mediated binding and degradation of TPO by platelets and, in all likelihood, megakaryocytes.