1 alpha, 25-Dihydroxyvitamin D3 (VD) is a potent inducer of monocytic differentiation of both normal and leukemic cells. Its effects are mediated by its nuclear receptor (VDR). Efficient gene activation requires the heterodimerization of VDR with Retinoid X Receptors (RXR). In the present study using specific antibodies, we analyzed the expression of the RXR alpha protein in blood mononuclear cells from acute myeloid patients (AML) (10 cases) and from myelomonocytic cell lines arrested at different stages of differentiation. We observed that the RXR alpha expression increased during myelomonocytic differentiation, since the highest levels were found in AML samples and in myelomonocytic cell lines having the highest amounts of monocytic precursors. We also demonstrated that fresh leukemic cells, whatever their stage of differentiation, as well as myelomonocytic cell lines, respond to VD by an increase in RXR alpha levels. Combinations of all-trans retinoic acid (RA) and VD, in some cases, increased this effect. This response suggests the involvement of RXR alpha in monocytic differentiation upon VD treatment.