In spite of their apparently restricted differentiation potentiality, hematopoietic precursors are plastic cells able to transdifferentiate from a maturation lineage to another. To better characterize this differentiation plasticity, we purified CD14À and CD14 þ myeloid precursors generated by 'in vitro' culture of human CD34 þ hematopoietic progenitors. Morphological analysis of the investigated cell populations indicated that, as expected, they consisted of granulocyte and monocyte precursors, respectively. Treatment with differentiation inducers revealed that CD14À cells were bipotent granulo-monocyte precursors, while CD14 þ cells appeared univocally committed to a terminal macrophage maturation. Flow cytometry analysis demonstrated that the conversion of granulocyte precursors to the mono-macrophage maturation lineage occurs through a differentiation transition in which the granulocyte-related myeloperoxidase enzyme and the monocyte-specific CD14 antigen are coexpressed. Expression profiling evidenced that the observed trans-differentiation process was accompanied by a remarkable upregulation of the monocyte-related MafB transcription factor.