The hematopoietic growth factors granulocyte-macrophage colony stimulating factor and steel factor have been shown to synergize in the stimulation of proliferation of the human factor-dependent cell line M07e. We investigated the possible involvement of lpid-mediated signaling in granulocyte-macrophage colony stimulating factor and steel factor induced proliferative synergism. It was found that treatment of M07e cells with these factors alone stimulates choline lipid metabolism and that they cooperate to further enhance this effect. Therefore a choline lipid signal transduction pathway may operate as part of the series of events leading to synergistic growth induced by the combination of granulocyte-macrophage colony stimulating factor and steel factor.