Transforming growth factor-alpha (TGF alpha) is a polypeptide that stimulates gastric epithelial cell proliferation and inhibits gastric acid secretion. Effects of TGF alpha are mediated by the epidermal growth factor receptor (EGFR). A recent study has shown the importance of TGF alpha in repairing gastric mucosa. Mucosal repair requires both proliferation and migration of a variety of cells, dependent on the depth of injury. We studied the effect of TGF alpha on cell migration and proliferation using well-established rabbit gastric epithelial monolayered cells. TGF alpha enhanced cell migration at 24 h or later. However, TGF alpha had already stimulated tritiated thymidine (3H-TdR) incorporation into DNA of gastric epithelial cells at 18 h, suggesting that the promotional effect of TGF alpha on cell migration is a result of stimulated cell proliferation. In addition, co-incubation of TGF alpha with hydroxyurea, which inhibits DNA synthesis, abolished the promotional effect of TGF alpha on cell migration. These results indicate that TGF alpha's promotional effect on cell migration is secondary to its stimulatory effect on cell proliferation.