The peptide neurotensin (NT) is an important intestinal hormone that affects gastrointestinal (GI) secretion, motility, and growth. This review describes the effects of NT in the GI tract and the distribution and localization of the gene encoding NT (i.e., NT/N). In addition, the molecular regulation of NT/N gene expression is discussed with special emphasis on the transcription factors, signal transduction pathways, and the role of gene methylation in modulating NT/N gene expression. Our studies have identified the NT/N gene as an excellent molecular model by which to define factors regulating intestinal cell differentiation. The in-depth analysis of the cellular processes leading to the expression of "model" intestinal genes, such as NT/N, can provide better understanding of normal gut development and function as well as defining more clearly the cellular events leading to gut neoplasia.