PURPOSE: The aim of this study was to examine the expression of HLA-DR surface antigen in undifferentiated human umbilical cord blood (hUCB) derived mesenchymal stem cells (MSCs) and after osteogenic, chondrogenic, and adipogenic differentiation. MATERIALS AND METHODS: hUCB-derived MSCs were differentiated into osteogenic, chondrogenic, and adipogenic lineages. Differentiation was assessed by immunohistochemical staining and RT-PCR. The expression of HLA-DR was assessed with antihuman HLA-DR antibody in undifferentiated hUCB-derived MSCs and after tri-lineage differentiation. RESULTS: HLA-DR expression was negative in undifferentiated hUCB-derived MSCs and after osteogenic and adipogenic differentiation. However, HLA-DR surface antigen was expressed after chondrogenic differentiation. CONCLUSION: The immunologic properties of hUCB-derived MSCs differ from known reports on bone marrow derived MSCs from the results of this study. Careful immunological survey seems to be needed in case of considering the transplantation of hUCB-derived MSCs differentiated into chondrocytes or cartilaginous tissue.