Various animal models have often been utilized as the basis of studies of the pathophysiology of peptic ulcer disease, however the ultrastructural changes in the evolution of duodenal ulcers produced in experimental animals have not been well elucidated. Utilizing a surgical method developed for the study of gastric ulcers we have established an experimental duodenal ulcer production technique in the rat which is highly reproducible and readily standardized. In the following time sequence study of experimental duodenal ulcers we present the ultrastructural features of ulcer induction and evolution.Duodenal ulcers were produced in 150-200 gram male Sprague Dawley rats by application of 50% acetic acid for 30 seconds through a 3 mm polyethylene tube to the serosa 1.0-1.5 cm distal to the pyloric sphincter. Routine transmission and scanning electron microscopy were performed on duodenal specimens at specific time points subsequent to surgical ulcer generation. Thin sections were stained with uranyl acetate and lead citrate and examined with a Phillip's EM 300 transmission electron microscope. For SEM, specimens were post-fixed in 2% osmium for two days, coated with gold/palladium and examined with JEOL JSM-6100 scanning electron microscope (JEOL, Inc., Peabody, MA).