Aspirin and other non-steroidal anti-inflammatory drugs are associated with gastritis and mucosal injury. The present study examined the efficacy of the synthetic prostanoid, Ro 22-1327, as a mucosal protectant against aspirin. Dogs were orally administered either vehicle followed by 650 mg of aspirin, or Ro 22-1327 followed one hour later by 650 mg of aspirin. Two hours later the dogs were endoscoped and lesions were scored. In separate dogs, with gastric pouches, acid secretion stimulated by food was monitored in the absence and presence of Ro 22-1327 for four hours. There were no gastric lesions in the dogs treated with the vehicle (polyethylene glycol 400; PEG) for Ro 22-1327 followed by vehicle (carboxymethylcellulose) for aspirin. Dogs dosed with PEG followed by aspirin had gastric lesions: mean (+/- S.E.) scores were 2.16 +/- 0.24 and 2.75 +/- 0.18 for the antrum and body, respectively. Ro 22-1327 provided protection from aspirin-induced injury. Significant (P less than 0.01) protection occurred at 1.0 mcg/kg of Ro 22-1327 in the antrum (0.60 +/- 0.40) and body (1.60 +/- 0.40). An oral dose of 10 mcg/kg did not inhibit peak or total food-stimulated gastric acid output. Ro 22-1327 is a potent mucosal protectant against aspirin-induced mucosal injury and this activity is not dependent upon inhibition of gastric acid secretion.