Epidermal growth factor (EGF) is mitogenic to gastric mucosal cells, protects against gastric mucosal injury induced by ulcerogenic agents, and stimulates cell migration in many systems. Restitution, the rapid re-establishment of mucosal integrity following damage, involves epithelial cell migration and can be monitored by measuring the transmucosal potential difference (PD) of tissue mounted in an Ussing chamber. The role of EGF in restitution is poorly characterized. To assess the effect of exogenous EGF on restitution, samples of rat gastric mucosa were mounted in an Ussing chamber with a solution of 10 nM EGF bathing either the mucosal or serosal surface. Matched control tissues from the same animals were untreated. Mucosal damage was induced by exposure of tissues to hyperosmolar sodium chloride. Restitution following injury was monitored by measuring the recovery of transmucosal PD, which reflects the degree of mucosal integrity. Undamaged mucosa maintained a PD of approximately -30 mV for several hours (mucosa negative with respect to serosa). Mucosal exposure to 1.2 M NaCl for 2 min reduced the PD to near 0 mV. Thereafter, the PD returned in approximately 60 min to plateau at a value representing maximal recovery. Tissues mucosally treated with 10 nM EGF recovered following damage to a maximum of 60.2 +/- 5.1% of pre-exposure PD, while matched controls recovered to only 46.2 +/- 5.8%, a significant difference. Tissues serosally treated with EGF recovered to 61.0 +/- 3.2% and matched controls recovered to 51.1 +/- 2.9%, also a significant difference. These results suggest that both serosally and mucosally applied EGF stimulates the restitution of rat gastric mucosa in vitro.