The mechanisms that regulate developmental control of the expression of MHC class I genes during generation of extra-embryonic tissues are largely unknown. In the present study, we studied the levels of transcripts of the human HLA-B27 gene in extra-embryonic tissues of transgenic mice containing the HLA-B27 (heavy chain) gene by in situ hybridization with biotinylated single-stranded RNA probes. In contrast to extra-embryonic stromal cells and embryonic tissues which contain (varying levels of) messenger RNA coding for HLA-B27, specific transcripts were not detected in labyrintho-, or spongiotrophoblast, nor in trophoblastic giant cells. These cells are devoid of HLA A and B locus class I transcripts in man. Regulation of expression of human MHC class I genes in extra-embryonic trophoblast in transgenic animals is thus under conserved selective pressure that is retained across a species barrier. Thus, in extra-embryonic tissues, regulation of expression of MHC class I genes is distinct from the mechanisms operating in developing embryonic cells.