Human leukocyte antigen (HLA)-G is a human nonclassic major histocompatibility complex (MHC) molecule characterized by a limited polymorphism and a low, restricted cell surface expression. HLA-G is constitutively expressed on trophoblasts, fetal endothelial, and epithelial cells, conferring alloimmune protection during pregnancy. HLA-G is also expressed in some malignancies and on macrophages and dendritic cells (DC) in tumoral and inflammatory diseases. Because DC constitute an important component in the immune response and umbilical cord blood has a different immune behavior than peripheral blood, the HLA-G protein profile and mRNA expression were investigated on the different DC subsets present in cord blood. Surface and intracellular expression have been reported on DC and HLA-G1, -G2, -G5, -G6, and -G7 transcripts were present. Different levels of soluble HLA-G were obtained from serum and correlated with gene expression. These data are in contrast with the data previously described for adult peripheral blood, where a limited pattern of HLA-G transcripts was reported; only in the maturation process were more isoforms present. These results demonstrate that DC from cord blood have a different behavior than DC in peripheral blood and could be in accordance with the results obtained in cord blood transplantation, where a lesser effect of graft-versus-host disease exists than in bone marrow transplantation.