HLA-G belongs to the non-classical HLA class-I family of genes presently designated as class-Ib genes. There are four membrane-bound (HLA-G1 to -G4) and three soluble forms (HLA-G5 to -G7) generated by alternative splicing of the primary transcript. HLA-G in the soluble form is found in the plasma, amniotic fluid, and cord blood of healthy individuals. Quantitative determination suggested that HLA-G levels are genetically controlled. While quantifying soluble HLA-G by ELISA, we observed that when plasma and serum levels were measured for the same individual, HLA-G plasma values were almost invariably higher than those from serum. Our results suggest that HLA-G is trapped and/or consumed during clot formation. The amount trapped within the clot is variable and inconsistent. To obtain values which reflect the true biological levels, it is therefore recommended that HLA-G should be determined in the plasma. If serum levels are determined, they should be compared with matched control sera. It should always be borne in mind that conclusions concerning sera levels might be erroneous, because the true plasma level of the protein can be significantly higher.