To find out whether non-steroidial anti-inflammatory drugs (NSAIDs) inhibit the proliferation of mucosal cells that normally leads to healing of gastric ulcers a microdissection technique was used to quantify mitosis in gastric glands at the ulcer edge in relation to that in the adjacent mucosa. The regeneration index thus obtained of the ulcer edge was greater in the 9 subjects with gastric ulcers not taking NSAIDs (mean index 3.1 [SEM 0.61]) than that in the 8 patients taking NSAIDs (index 1.49 [0.16]). In rats in which gastric ulcers were produced with a cryoprobe, the ulcers were larger and slower to heal in those receiving indomethacin than in controls; also, immunohistochemical staining indicated significantly fewer mitotic cells in glands adjacent to the ulcer in indomethacin-treated rats (8 mitoses [SEM 3]) than in control animals (25 ). The prostaglandin E1 analogue misoprostol reversed the inhibition of healing and substantially restored the proliferative rate in the animals. Inhibition of epithelial cell division normally involved in gastric ulcer healing would contribute to the high prevalence of gastric ulcer during NSAID therapy.