Transcriptional regulation of the immunoglobulin (Ig) genes is one of the best-studied systems for understanding tissue-restricted gene control. Dissection of the Ig genes reveals that each contains multiple regulatory elements that are preferentially active in B lymphocytes. These include a promoter and one or more enhancer elements. Biochemical analysis and cloning of the genes for transactivator proteins has uncovered a variety of distinct proteins that are often members of gene families. The transactivators themselves are under complex regulation at the transcriptional level as well as by interactions with other proteins in the cell. It appears that the coordinate action of a select constellation of these transactivators conveys the information for tissue-specific expression of the Ig genes.