We investigated the effect of dexamethasone on indomethacin-induced ulceration in the rat. Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1, 3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically. Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched-out and haemorrhagic while the ulcers arising in rats pre-treated with dexamethasone (all doses) were 'plugged' by a white fibrino-purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine. We report the observation that dexamethasone at high doses inhibits indomethacin-induced jejunal ulceration in the rat while at low doses it promotes 'plugging' of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.