Misoprostol, a synthetic prostaglandin E1, analog, is effective in treating and preventing nonsteroidal antiin-flammatory drug (NSAID)-induced gastrointestinal lesions in humans. The effectiveness of misoprostol in preventing aspirin-induced gastroduodenal injury was studied in 3 groups of 6 adult mixed breed dogs. Group I received 3 μg/kg misoprostol PO tid. Group II received 3 μg/kg misoprostol PO tid and 35 mg/kg aspirin PO tid. Group III received 35 mg/kg aspirin PO tid. Endoscopy was performed on days 0, 5, 14, and 30. Five regions of the upper gastrointestinal tract were qualitatively scored from 1 to 12 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving a higher numerical score than submucosal hemorrhage. A total score was assigned based on the sum of the scores from all regions. Comparisons among groups on each day were performed using the Kruskal-Wallis test. Differences within a group among different time periods were determined using appropriate multiple comparisons. Significant difference in mean gastroduodenal lesion score was found among all groups at 5, 14, and 30 days. Mean total score on days 5, 14, and 30 were as follows: group 1,5.0,5.2, 9.0; group II, 12.0, 12.7, 16.2; and group III, 26.0, 23.8, 21.5, respectively. Significant differences within a group among different time periods were found from days 0 to 5 in groups I and II, and from days 14 to 30 in group I. It was concluded that misoprostol effectively decreased endoscopically detectable mucosal lesions in dogs given aspirin.