Megakaryocyte progenitors are notable for their response to synergistic cytokine combinations and apparently early position in the hematopoietic differentiation pathway. Although high-proliferative-potential murine megakaryocyte progenitors have been described, they have previously been primarily observed as unilineage colonies. We describe a subclass of agar-based high-proliferative-potential colony forming cells (HPP-CFC) derived from populations enriched for early hematopoietic progenitors which, when stimulated with the combination of CSF-1, G-CSF, GM-CSF, IL-1 alpha, IL-3 and SCF, produces colonies with trilineage potential for macrophages, granulocytes, and megakaryocytes. The high proliferative potential megakaryocyte mixed (HPP-Meg-Mix) colony-forming cell is defined as a cell meeting traditional criteria for HPP-CFC but additionally containing 20 or more megakaryocytes per colony. The combination of high-proliferative-potential, multilineage differentiation, and megakaryocytic lineage capacity suggests that the HPP-Meg-Mix marks a very early hematopoietic progenitor cell.