A decoction of Mikania cordata (Compositae) is commonly used for the treatment of gastric ulcer in the Rajbari district of Bangladesh. We have evaluated the anti-ulcerogenic effect of the alkaloidal fraction from the whole plant of M. cordata on diclofenac sodium-induced gastrointestinal lesion in rats. Long Evan's rats were divided into five groups. The control group was kept undisturbed. The vehicle group received vehicle after a 48-h fast. The diclofenac group received diclofenac sodium suspension (80 mg kg(-1)) after a 48-h fast. The diclofenac-ranitidine group (anti-ulcer drug used as a standard) received 35 mg kg(-1) ranitidine hydrochloride suspension 1 h after diclofenac sodium administration, after a 48-h fast. The diclofenac-extract group received alkaloidal fraction (50 mg kg(-1)) 1 h after diclofenac administration, after a 48-h fast. The biochemical, morphological and histological changes were studied. The data showed that the pH values of the stomach and duodenum were increased significantly (P < 0.001) in the alkaloidal-administered group compared with the control group (3.09 +/- 0.0429 vs 2.07 +/- 0.0339 and 6.79 +/- 0.1162 vs 6.19 +/- 0.1273, respectively). There were significant changes (P < 0.001) detected in the morphological study. The ulcer index of the stomach (0.268 +/- 0.0346) and of the duodenum (0.050 +/- 0.0129) in the alkaloidal-administered group were significantly lower than the diclofenac-only administered group (0.691 +/- 0.0184 and 0.0933 +/- 0.0138, respectively). According to the grading of tissue damage in the histological study, there were less or no lesions on the gastrointestinal mucosa of the alkaloidal-administered group compared with the diclofenac-only group (0 vs 5, respectively). When the results of the alkaloid extract group where compared with the ranitidine hydrochloride group a similar or more potent effect was observed with the alkaloidal extract group. The results of this study revealed that the bioactive principles of M. cordata have anti-ulcerogenic effects. The results validate the traditional use of this plant for the treatment of gastric ulcer in Bangladesh.