HLA-G antigens are highly expressed in maternal peripheral blood during early pregnancy in transgenic mice. In this study, we determined the levels of HLA-G in white blood cells during early pregnancy and after interruption of pregnancy in triple transgenic mice (H-2Kb/HLA-G, hβ2m, and hCD2/hCD8-TRI). The pregnancies were interrupted on day 7 using the anti-progesterone agent mifepristone (RU486). Blood samples of 20 pregnant TRI mice were taken and the HLA-G levels were determined on days 2, 4 and 6 of pregnancy and on days 9, 11 and 13 after fertilization. The monoclonal antibody W6/32, specific for monomorphic determinant HLA class I molecules, was used in combination with an immunolocalization method using a photonic microscope. The HLA-G levels increased gradually on days 2, 4 and 6 of pregnancy, and the interruption of pregnancy on day 7 was followed by a decrease of HLA-G levels. The data indicate that pregnancy is characterized by the early presence of HLA-G in maternal peripheral blood in TRI transgenic mice and suggest that HLA-G may serve as a useful indicator for pregnancy maintenance and well-being.