The expression of the nonclassical MHC class Ib molecule HLA-G is nearly exclusively restricted to the feto-maternal interface during pregnancy. There it probably serves the same physiological functions already known for classical MHC class I molecules; these include peptide presentation, natural killer cell (NK) inhibition and probably also T cell restriction. In this study a comparison between HLA-G and HLA-A2 as far as the amount and complexity of bound peptides is concerned revealed no significant differences. The peptide motif of HLA-G, as determined by analysis of naturally eluted peptides allows the construction of a peptide library that is efficient in binding to HLA-G and thereby confirms the rules of peptide binding to this nonclassical MHC class I molecule. In addition, we demonstrate that the inhibition of NK cells by HLA-G varies remarkably among the NK repertoires of different donors. The function of HLA-G as a survival factor in the development of the fetus during pregnancy is discussed in detail.