The effect of Azadirachta indica extract on gastric ulceration was studied in albino rats. Azadirachta indica extract (100-800 mg/kg p.o., 100-25 mg/kg i.p.) significantly inhibited gastric ulceration induced by indomethacin (40 mg/kg). Administration of 800 mg/kg p.o. and 250 mg/kg i.p. caused 100% cytoprotection against indomethacin (40mg/kg, i.p.)-induced gastric ulceration. This action was accompanied by a dose-dependent decrease in total gastric acidity. In order to investigate the probable mechanism of Azadirachta indica antiulcer activity, the effect of the extract alone and in combination with histamine (1mg/kg) and cimetidine (0.12 mg/kg) on gastric acid secretion in situ was studied. Azadirachta indica (250 mg/kg) significantly inhibited the basal and histamine-induced gastric acid secretion. Cimetidine seemed to augment Azadirachta indica inhibition of gastric acid secretion. The results suggest that the stem bark extract of Azadirachta indica possesses antiulcer agents, which probably act via histamine H(2) receptor.