OBJECTIVE To determine the ontogeny of major histocompatibility complex (MHC) expression and TAP products in mouse embryos. METHODS mRNAs encoding MHC and associated molecules were identified by reverse transcriptase-polymerase chain reaction, and the protein products were localized by confocal microscopy. RESULTS mRNAs encoding class Ia (H-2Db) and class Ib (Q7/9) were present in one-cell embryos, whereas beta 2-microglobulin (beta 2-m) transcripts were not detected until the two-cell stage. Transporter TAP1, but not TAP2, transcripts were detected only in blastocysts. H-2 class Ia (classical) protein was detected on the surface of two-cell embryos, H-2 class Ib (nonclassical) protein was detected on one-cell embryos, and beta 2-m transcripts were detected on eight-cell embryos; TAP1 protein was present at low levels in the cytoplasm from the one-cell stage onward, increasing in expression in blastocysts. CONCLUSIONS In mice, MHC class I mRNAs encoding the heavy chain of H-2- and Q7/9-encoding Qa2 molecules are synthesized soon after conception prior to implantation. Similarly, the nonpolymorphic MHC class I-associated molecule beta 2-m also is expressed before implantation. TAP1, but not TAP2, is first detected at the blastocyst stage, thus preceding the onset of TAP2 in embryonic development.