Enprostil, a synthetic analogue of prostaglandin E2, is known to be a potent inhibitor of gastric acid secretion, and has marked anti-ulcer activity in rodents. Enprostil was administered in doses ranging from 15 to 250 micrograms/kg to rats prepared using the Shay procedure. Three hours later, the rats' stomachs were removed and processed either for the chemical determination of mucus, or for scanning electron microscopy. For the chemical determination, the secreted gastric juice was removed and the adherent gastric mucus was eluted with 2 M sodium chloride. The anthrone method was used to determine the mucus present. Enprostil was found to significantly increase gastric mucus at a dose of 60 micrograms/kg when measured by the anthrone test. Enprostil administered by the oral route was most effective in stimulating mucus secretion, suggesting a local or topical action of enprostil on mucus-secreting cells. Scanning electron microscopy of rat fundic mucosa after enprostil administration (50 to 100 micrograms/kg) revealed the presence of thin veil-like layers covering the epithelial surface, which was interpreted as an increase in mucus secretion. Higher magnifications (X 2,000) clearly showed the layers of mucus covering the surface epithelial cells. Enprostil's apparent increase of gastric mucus secretion may contribute to its anti-ulcer activity and may promote gastric healing.