The chemokine stromal-derived factor-1α (SDF-1α) and its receptor CXCR4 are critically involved in directional migration and homing of plasma cells in multiple myeloma. Here, we show that the expression of SDF-1α and CXCR4 was significantly down-regulated in patients treated with thalidomide (n=10) as compared to newly diagnosed MM patients (n=31) and MM patients treated with other drugs (n=38). SDF-1 α and CXCR4 expression was also significantly decreased in a RPMI 8226 cell line treated with 10 and 20μmol/L of thalidomide. Our findings indicate that thalidomide therapy induces down-regulation of CXCR4 and its ligand SDF-1α in multiple myeloma.