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The gastric mucosa maintains its integrity despite the harsh environment of an acidic luminal pH and strong mechanical stresses secondary to peristalsis of ingested contents. The mucosa has marshalled a battery of both protective and reparative mechanisms which, in general, prevent the deleterious effects of these factors that, if unchecked, may result in untoward consequences such as gastritis and peptic ulcer disease. An increasing body of evidence suggests that transforming growth factor-alpha (TGF alpha) produced by the gastric mucosa is a critical mediator of gastric mucosal homeostasis. TGF alpha inhibits acid secretion, stimulates mucosal restitution after injury (cell migration and proliferation), and augments gastric mucin levels. We review the data that support a role for this endogenously produced growth factor in both protective and reparative actions in the stomach. In addition, we discuss a possible role for overproduction of TGF alpha in the pathogenesis of Ménétrier's disease, a premalignant disorder of the stomach characterized by fundic gland hyperplasia, hypochlorhydria, increased gastric mucus, and hypoalbuminemia.