Human granulocytic ehrlichiosis (HGE) is an emerging tickborne infection resulting in an acute febrile illness associated with cytopenias and characteristic intracellular organisms within peripheral blood granulocytes. The etiologic agent of HGE has recently been isolated and cultivated in the HL-60 promyelocytic leukemia cell line, but the spectrumof host cells that it naturally infects remains unknown. To determine if normal hematopoietic progenitors could be targets of infection, CD34/ primary human bone marrow cells, stimulated to differentiate along myelomonocytic lineages, were incubated with the HGE agent. Immature marrowprogenitors and, remarkably, not only granulocytic but also CD14/ monocytic cells fromthese cultures supported replication of the HGE agent, suggesting that all are potential targets of infection in vivo. Infection of bone marrowprogenitors may contribute to the hematologic manifestations of HGE. Furthermore, the ability of the agent to interact with monocytes has significant implications regarding disease pathogenesis and host response.