The expression of the class-II antigens of the major histocompatibility complex is tissue-specific, developmentally regulated in cells of the B lineage, and inducible by cytokine. Some of the molecular mechanisms that account for this regulation have recently been elucidated. DNA sequences upstream of human and mouse class-II genes that are critical for the transcription of these genes have been identified through transfection studies and transgenic analysis. Furthermore, a number of transcription factors that bind to important promoter motifs have recently been isolated. Examination of the class-II promoter in vivo both in the normal state and in patients with bare lymphocyte syndrome has further increased our understanding of class-II regulation.