Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1α,25-Dihydroxyvitamin D3 the active form of Vitamin D 3 (D3) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D3 and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable with that of immature DCs. But in contrast to immature DCs, D3/Dex exposed DCs secrete IL-10 and show upregulated transcription of mRNA encoding the Ig-like inhibitory receptor ILT4. D3/Dex exposed DCs also inhibit alloreactivity and slightly enhance the degree of apoptosis in mature DCs. Thus, D3/Dex is an effective immunosuppressive drug combination for the induction of DCs capable of inducing T cell hyporesponsiveness. © 2003 Elsevier B.V. All rights reserved.