To assess the effects of various nonsteroidal antiinflammatory drugs on gastroduodenal mucosa, 72 normal men were administered either etodolac, indomethacin, ibuprofen, naproxen, or placebo for 7 days. Gastric and duodenal mucosa were scored before and after treatment by direct endoscopy and evaluation of photographs taken during endoscopy. Subjects treated with indomethacin, ibuprofen, and naproxen had significantly worse direct gastric scores, and those treated with indomethacin and naproxen also had significantly worse direct duodenal scores, when compared with pre-treatment and placebo scores. Subjects given either of 2 doses of etodolac had gastric and duodenal scores comparable to pretreatment and placebo scores. The direct gastric scores of the etodolac groups were significantly better than the scores of subjects receiving indomethacin, ibuprofen and naproxen. Similar results were obtained when endoscopy photographs were scored.