Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. In restitution, epithelial cells near the wound rapidly flatten, extend lamellipodia, and migrate to reform an intact epithelial barrier. The signaling pathways responsible for controlling these processes are poorly understood. Multiple lines of evidence suggest the direct involvement of the mitogen-activated protein (MAP) kinase signaling pathways in restitution. Cytokines that augment epithelial wound repair generally have in common the ability to activate the MAP kinase pathway involving Ras and extracellular signal-regulated kinase (ERK). Ras function is necessary for efficient migration following wounding. Tissue injury results in the rapid expression of immediate response genes including c-Fos and c-Jun. Activation of the MAP kinase pathways of ERK and c-Jun amino-terminal protein kinase is known to directly activate these immediate response genes and thus provides a potential mechanism for transcriptional regulation of other genes necessary for restitution and wound repair.