To gain additional informations on the role played by Natural Killer cells (NK) in the differentiation of human hematopoietic precursors, we have studied the effect of NK-cell depletion on the in vitro proliferation of hematopoietic cells. NK cells were depleted from blood mononuclear cells by FACS using anti CD3 and anti CD56 monoclonal antibodies. Depletion of NK cells suppressed CFU-GM up to 69% (P < 0.01), while no significant effect on either BFU-E and CFU-Mix growth was observed. To define the threshold of CD56+ cells required to support CFU-GM formation, NK cells were added to NK-depleted cells in a titrated fashion. Enhancement of CFU-GM colony growth was observed at NK/NK- depleted cells ratio of 0.15/1. A dose dependent suppression of CFU growth was observed at ratios ranging from 0.25/1 to 0.5/1. Addition of neutralizing antibodies against IL3 and GM-CSF abrogate the stimulating effect of NK cells. Our results suggest that cells with LGL morphology and NK markers play an important role in differentiation of myeloid precursors and exert a moderate influence on erythroid progenitors. The modulatory effect on hematopoietic progenitors depend on the number of NK cells present in the mixed culture.