The human MHC class I chain-related genes (MICA and MICB) are located within the HLA class I region of chromosome 6. Their organization, expression and products differ considerably from classical HLA class I genes. MIC proteins are considered to be markers of ‘stress’ in the epithelia, and act as ligands for cells expressing a common activatory natural killer-cell receptor (NKG2D). Molecular models are now available for the MICA protein, both bound and complexed with NKG2D. MICA molecules appear to be highly flexible and polymorphic, although the functional relevance and implications of their polymorphism have yet to be fully discerned.