Prostaglandins are presumed to have many cytoprotective properties that play a role in the pathogenesis of duodenal ulcer and its complications where decreased levels of prostaglandin E2 (PGE2) impair gastric motility, oppose ionic membrane influx, and enhance obstructive changes. These are just some of the mechanisms that may cause pyloric obstruction and may result from decreased PGE2 levels. To evaluate this hypothesis, 17 patients with duodenal ulcer complicated by pyloric stenosis were examined. Biopsy specimens were obtained from the duodenal bulb, ulcer margins, gastric antrum, fundus, and gastric secretions. Prostaglandin E2 levels were measured and compared with those taken from the same areas during a second endoscopy in a later quiescent or exacerbated phase. During the active phase of pyloric stenosis, decreased levels of PGE2 were found in the gastroduodenal tissues and secretions were compared with levels found during convalescence. These level differences were statistically significant. A correlation between the severity of the clinical and endoscopic findings and the PGE2 levels was found. A further decrease in PGE2 levels in the second endoscopy were indicative of the presence of scar tissue, representing an irreversible obstructive peptic disease.