This chapter describes tissue-specific control of genes through the reintroduction of cloned genes into animals. It focuses on the expression of a family of pancreas-specific genes, the pancreatic serine proteases, because of the advantages that accrue from the comparative analysis of similarly regulated genes. An understanding of transcriptional regulation includes an understanding of the nature of DNA control sequences associated with regulated genes, the number and nature of trans acting factors that interact with those sequences, the nature of that interaction, and the way that interaction then modulates gene transcription. cis Acting regulatory information sufficient for pancreas specific expression in animals is contained within the short elastase I gene sequence between –205 and +8. This gene region confers transcriptional specificity in transgenic mice bearing the elastase–human growth hormone (hGH) fusion gene because pancreatic nuclei, and not hepatic nuclei, synthesize hGH RNA. Moreover, the transcription of the elastase–hGH fusion gene correlates with a pancreas specific DNase I hypersensitive site within the elastase I regulatory region.