When myeloblastic ML1 cells were cultured in the presence of Vitamin K2 (menaquinone, VK2), the population of cells capable of reducing NBT increased to 83.5% at low VK2 concentration of 1 microM, indicating VK2 induces cellular differentiation. VK2 also exerted differentiation-inducing action on histiocytic U937 and promyelocytic HL60 cell lines. None of these effects were observed with Vitamin K1 (phylloquinone, VK1), suggesting the geranylgeranyl group of the side chain of VK2 to be essential to these effects. Combinations of VK2 with other differentiation-inducers such as interferon-gamma, retinoic acid, or camptothecin additively or synergistically induced the differentiation of HL-60 cells. These results suggest that VK2 may safely be used in differentiation therapy in combination with other inducers.