AbstractNonsteroidal antiinflammatory drugs (NSAID) and ethanol can produce gastritis and mucosal hemorrhages in man. We report the potent protective effects of a synthetic prostanoid, Ro 22‐1327, on experimental models of NSAID and ethanol‐induced gastric mucosal injury. Rats were orally administered aspirin (200 mg/kg in 150 mM HCl), indomethacin (80 mg/kg), or absolute ethanol (1 ml) after pretreatment with vehicle or Ro 22‐1327. Oral administration of 10 μg/kg and 100 μg/kg of Ro 22‐1327 significantly (P≤ ·05) protected the gastric mucosa from the corrosive effects of aspirin and ethanol; Ro 22‐1327 protected against indomethacin at a dose of 100 μg/kg. The duration of the protective effect was 90 and 180 min for aspirin and ethanol, respectively. Topical (dermal) application of 100 μg/kg and intraperitoneal injection of 1 μg/kg and 100 μg/kg of Ro 22‐1327 produced significant (P≤ ·01) inhibition of the formation of ethanol‐induced lesions. Orally administered Ro 22‐1327 produced a significant (P≤ ·001) dose‐related (25 μg/kg–225 μg/kg) increase (40–90%) in mean thickness of mucus covering the gastric mucosa. PGE2was less effective than Ro 22‐1327. Ro 22‐1327 produced diarrhea only when administered orally at doses that were 100‐fold greater than the dose required for mucosal protection. The results suggest that this new prostanoid may be useful as adjunctive therapy in rheumatoid arthritic patients susceptible to gastritis and mucosal injury cau