This article presents an overview of the more recent data dealing with the constitutive expression of classical HLA-A, -B, -C and nonclassical HLA-E, -F, -G class I genes in the different trophoblast cell subpopulations that constitute the materno-fetal interface during human pregnancy. Although transcribed, classical HLA class I genes are never expressed as membrane-bound products in any of the trophoblast cell subpopulations. On the contrary, HLA-G is expressed at the cell surface of extravillous cytotrophoblast cells from first trimester placenta, suggesting that it may play a role in the maternal tolerance against the fetal allograft. Molecular regulatory mechanisms that may control such differential expression of classical and nonclassical class I molecules, according to the cell type, state of differentiation and stage of gestation are also examined. They may operate at the levels of transcription (cis- and/or trans-acting mechanisms), translation and/or transport of HLA class I heavy chains to the cell surface.