Gene expression in the intestine exhibits complex patterns during development, along the horizontal and vertical axes of the adult intestine, and in adaptation to pathophysiologic events. The recent cloning of the complementary DNAs and genes for a variety of intestine-specific proteins has provided critical reagents to study gene expression in the intestine in normal physiology and in diseased states. These investigations have begun to reveal several different strategies for intestine-specific gene regulation, including novel DNA-binding proteins that interact with the genes, the use of alternative intestine-specific promoters, and repressors of gene expression in nonintestinal cells. Additional studies have used molecular biologic approaches to characterize the mechanisms for regulating the production of intestinal proteins, such as by modulating gene transcription, translation, or posttranslational modifications. Finally, new insights have been provided into the molecular defects in human inherited diseases, including the identification of a point mutation in patients with glucose-galactose malabsorption.