This review focuses on recent progress made in MHC regulation. The better characterization of proteins that interact with MHC class I and II promoters and the isolation of genes encoding several of these transcription factors, such as H-2RIIBP/RXR beta, NK kappa B, I-kappa B, hXBP-1 and NF-Y, allow the functional analysis of these molecules in MHC gene regulation. The application of new techniques, such as genomic in vivo footprinting analysis, to the study of these promoters provides insights into the status of in vivo protein-DNA interaction over these promoters. New insights have also been gained in the understanding of MHC-associated genes.