Galectin-1 is a member of the family of beta-galactoside binding animal lectins, galectins. Its presence in the bone marrow has been detected; however, its role in the regulation of hematopoiesis is unknown. In the present study, we have evaluated the effect of recombinant human galectin-1 on the proliferation and survival of murine and human hematopoietic stem and progenitor cells. We show that low amount of galectin-1 (10 ng/ml) increases the formation of granulocyte-macrophage and erythroid colonies and the frequencies of day-7 cobblestone area-forming cells on a lactose-inhibitable fashion. In contrast, high amount of galectin-1 (10 microg/ml) dramatically reduces the growth of the committed blood-forming progenitor cells as well as the much younger, lineage-negative hematopoietic cells (day-28 to -35 cobblestone area-forming cells). This inhibition is not blocked by lactose and, therefore, is largely independent of the beta-galactoside-binding site of the lectin. Furthermore, assays to detect apoptosis render it likely that the high amount of galectin-1 acts as a classical proapoptotic factor for the premature hematopoietic cells.