Prostaglandins protect the gastric mucosa against a variety of injurious agents and may accelerate the recovery of the gastric mucosa following damage. In previous studies prostaglandins were given prior to the injurious agent, so it was not possible to distinguish their potential effects on accelerating repair or reducing initial damage. We have investigated the effect of 16,16-dimethyl prostaglandin E(2) (dmPGE(2)) on the repair of the gastric muscosa after injury induced by several injurious agents. dmPGE(2) was given orally 15 min prior to aspirin or sodium salicylate, or 30 min after aspirin, sodium salicylate, or ethanol. dmPGE(2) delivered prior to injury reduced the aspirin-induced fall in mucosal potential difference (PD), but had no effect on that induced by sodium salicylate, dmPGE(2) administered after ASA injury significantly increased recovery of PD (P < 0.05), but did not alter the rate of recovery of PD with other damaging agents. Histological damage was decreased in rats treated with dmPGE(2) after aspirin compared to aspirin-only-treated rats (P < 0.02). Exogenous dmPGE(2) protects and restores gastric mucosal integrity after aspirin damage but has no effect on the repair of sodium salicylate and ethanol injured mucosa, suggesting that repair of the gastric mucosa after aspirin damage is enhanced by dmPGE(2) due to its ability to prevent ongoing damage, rather than directly enhancing repair processes.