Class II Major Histocompatibility Complex (MHC) products are essential initiators of cellular immune responses. Their cell surface expression demonstrates aspects of tissue-restricted, inducible, differentiation-dependent, and coordinate regulation indicative of complex molecular controls mediated primarily at the level of transcription. This article reviews our current understanding of transcriptional regulation of one such human class II MHC gene, DRA. Considerable effort has been exerted toward characterizing the cis-acting regulatory sequences and trans-acting DNA binding proteins responsible for regulating DRA transcription. Recent application of novel molecular techniques has resulted in the cloning and characterization of some of these regulatory proteins. A model is presented herein which accommodates the current knowledge of DRA gene regulation.