Thrombopoietin (TPO) is the major regulator of platelet production in vivo and is the ligand for the MPL receptor. In an effort to determine the distribution of TPO and MPL in the different hematopoietic cell types and in various types of tissue, we examined the mRNA expression of this ligand-receptor pair in two series of human leukemia-lymphoma cell lines and of solid tumor cancer cell lines using northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. At the northern blot mRNA level, 8/15 (53%) megakaryocytic and 3/11 (27%) erythroid leukemia cell lines expressed MPL mRNA; except for one positive monocytic cell line, the remaining 78 pre B-cell, B-cell, plasma cell, T-cell, NK cell, myeloid, monocytic and Hodgkin/anaplastic large cell lymphoma (ALCL)-derived cell lines were negative. No MPL message was detected in any of the 23 solid tumor cell lines established from 21 different tumors. In order to examine whether a low level of MPL expression could be detected, 51 leukemia cell lines were investigated with the RT-PCR technique. By this technique, MPL message was seen in many more cell types: 13/26 (50%) of non-erythromegakaryocytic cell lines and in nearly all megakaryocytic (14/15, 93%) and erythroid (10/11, 91%) cell lines. Thus, the highest expression of MPL clearly occurs in cells with megakaryocytic differentiation; furthermore, expression of MPL appears to be restricted to hematopoietic cell types. TPO mRNA expression was examined by RT-PCR and found in 9/11 (82%) of the solid tumor cell lines (derived from colon, endometrium, kidney, liver, ovary, retinoblastoma and urinary bladder cancers). Among the leukemia-lymphoma cell lines, TPO mRNA was detected by RT-PCR in most plasma cell, myeloid, megakaryocytic and erythroid cell lines, but not in pre B-cell, B-cell or T-/NK-cell lines. The results reported here extend the observations of MPL and TPO expression in normal cells to the whole spectrum of hematological cell types and to an array of different tissue types, both exemplified by their malignant counterparts.