Cytomegaloviruses (CMVs) represent prototypic viruses of the (i‐subgroup of herpesviruses, Murine cytomegalovirus (MCMV) infects mice as its natural host. Among viruses, CMVs have evolved the most extensive genetic repertoire to subvert MHC class I functions. To date three MCMV proteins have been identified which affect MHC I complexes. They are encoded by members of large virus‐specific gene families located at either flanking region of the 235 kb MCMV genome. The MHC I subversive genes belong to the early class of genes and code for type I transmembrane glycoproteins. The ml52‐encoded 37/40 kDa glycoprotein interacts with MHC I transiently and retains class I complexes in the endoplasmic reticulum (ER) Golgi intermediate compartment on its journey to the endolysosome. In contrast, the m06‐encoded glycoprotein of 48 kDa complexes tightly with ternary MHC class I molecules in the ER, Due to sorting signals in its cytoplasmic tail, gp48 redirects MHC I to endolysosomal compartments for proteolytic destruction. Likewise, the 34 kDa glycoprotein encoded by mO4 binds tightly to MHC class I complexes in (he ER but the gp34/MHC I complex reaches the plasma membrane. The CD8⁺ T‐cell‐dependent attenuation of a m152 deletion mutant virus proves for the first time that inhibition of antigen presentation is indeed essential for the biological fitness of CMVs in vivo.