Indomethacin produces gastric corpus erosions in the fasted rat and small intestinal ulcers in the conventionally fed rat. We found that in rats fed chow pellets for 1 h after a 24-h fast, indomethacin given within 2 h after refeeding produced lesions in the gastric antrum, primarily along the lesser curvature, and also in the small intestine. The antral lesions reached a maximum size in 6-10 h, penetrated the muscularis mucosae within 3 days, and did not diminish for at least 7 days. The formation of the antral ulcer was prevented by prostaglandins or adrenalectomy, but was not affected by cimetidine, atropine, and/or vagotomy. In contrast, the gastric corpus erosions produced by indomethacin in the fasted rat were prevented by antisecretory drugs or vagotomy, and were aggravated by adrenalectomy. It is concluded that: (a) the chronic antral ulcers produced by indomethacin in a refed rat mimic human gastric ulcer with regard to location and histology; and (b) the mechanism of antral ulcer formation is different from corpus erosion formation, in that it was resistant to antisecretory drugs and vagotomy and was prevented by adrenalectomy. This experimental ulcer model could prove useful for studies of the etiology and therapy of gastric ulcer disease.