Epidermal growth factor (EGF) is an important constituent of several gastrointestinal secretions. Many studies in both animals and humans have shown EGF to have multiple effects upon gut epithelial cells. These include cytoprotection, stimulatory effects on cell proliferation and migration, induction of gene expression such as mucosal enzymes and trefoil proteins, and inhibitory effects on gastric acid secretion. The main conundrum associated with EGF action is the disparity between experimental studies on its luminal and systemic actions. Opinion is sharply divided as to whether or not EGF has any action when given luminally and on the site of the EGF receptors on gut epithelial cells. Most studies agree that the EGF receptors are located on the basolateral surface, in which case EGF should only be active if surface ulceration has occurred—unless there is translocation across the epithelium. There are several clinical situations in which EGF might be useful in cytoprotection and in stimulating repair and regeneration in the gut. These include necrotizing enterocolitis and mucositis, and it is to be hoped that the solid basis of experimental studies on EGF might stimulate work on this topic. (Journal of Parenteral and Enteral Nutrition23:S83‐S88, 1999)