Thrombopoietin (TPO) is the primary hematopoietic growth let counts, the cells of the proximal convoluted tubules of factor involved in the regulation of platelet production. Al- the kidney showed consistent positive staining whereas the though the kidney, liver, bone marrow (BM), and spleen have signal in the cells of the distal convoluted tubules was less been identified as the major sources of TPO production, the consistent. Strong hybridization signal was also evident in precise cellular location of TPO mRNA expression in these the hepatocytes. The hybridization signal in the spleen, even tissues remains unknown. We have identified the cells ex- in thrombocytopenic subjects, was too weak to allow confipressing TPO mRNA in the human kidney, liver, and BM dent identification of the cells expressing TPO mRNA. In all using an in situ hybridization assay. In the BM of individuals subjects, the interstitial cells and endothelial cells of the liver with normal platelet counts, the hybridization signal was and spleen, the renal peritubular cells, and the hematopoitoo weak to allow identification of the TPO mRNA express- etic precursor cells of the BM showed no TPO mRNA expresing cells. However, in thrombocytopenic subjects with aplas- sion. Our data suggest that TPO mRNA expression in the tic anemia, postchemotherapy marrow aplasia, and immune human BM may be modulated by platelet mass. thrombocytopenia, the stromal cells showed strong TPO 1997 by The American Society of Hematology. mRNA expression. In the human subjects with normal plate-by administration of TPO. These observations suggest that