The murine class II genes are contained in the I region of the major histocompatibility complex (MHC). In the mouse, there are seven class II genes: A beta 3, A beta 2, A beta, E beta, E beta 2, A alpha, and E alpha. The A beta and A alpha genes code for the two polypeptide chains that form the I-A immune response molecule. The E beta and E alpha genes code for the two polypeptide chains that form the I-E immune response molecule. This review covers the genetic organization of the I region and the exon-intron structure of the class II genes. This review also discusses site-directed mutagenesis and exon shuffling studies and the effect of these changes on the function of Ia genes. Regulation of the cellular expression of Ia genes is discussed with emphasis on recent studies involving class II transgenic mice. Also, studies mapping recombination hotspots within the E alpha and E beta genes are reviewed.