Peptide binding proteins of the major histocompatibility complex consist of the "classical" class Ia and "nonclassical" class Ib genes. The gene organization and structure/function relationship of the various exons comprising class I proteins are very similar among the class Ia and class Ib genes. Although the tissue-specific patterns of expression of these two gene families are overlapping, many class Ib genes are distinguished by relative low abundance and/or limited tissue distribution. Further, many of the class Ib genes serve specialized roles in immune responses. Given that the coding sequences of the class Ia and class Ib genes are highly homologous we sought to examine the promoter regions of the various class Ib genes by comparison to the well characterized promoter elements regulating expression of the class Ia genes. This analysis revealed a surprising complexity of promoter structures among all class I genes and few instances of conservation of class Ia promoter regulatory elements among the class Ib genes.