A new isoform of the full-length murine thrombopoietin (Tpo) receptor was isolated from a murine spleen cDNA library. This isoform, c-mpl-II, differs from full-length c-mpl (c-mpl-I) by virtue of deletion of 180 nucleotides that encode 60 amino acids located in the extracellular domain of Mpl. Normal murine megakaryocytes were found to express both c-mpl-I and c-mpl-II transcripts. BaF3 cells transfected with c-mpl-I expressed a 95 kDa protein that was displayed on the cell surface and bound 125I-Tpo. BaF3 cells transfected with c-mpl-II expressed a 70 kDa protein. However, these cells were not able to bind 125I-Tpo and surface display of Mpl-II could not be detected. In summary, c-mpl-II is an isoform of murine Mpl expressed by megakaryocytes that lacks a 60 amino acid region required for surface expression of the protein.