Background: Little is known of pseudomembranous esophagitis, a condition of striking endoscopic appearance. Presented here is a description of its nature and outcome. Method: Information on all patients with upper GI disease seen in our unit are held in a computerized database that includes presentation, diagnosis (including pseudomembranous esophagitis), treatment, and outcome. Results: Forty-eight patients (mean age 70 years) with pseudomembranous esophagitis were seen over 15 years; 42 were in-patients with various illnesses. At endoscopy, a thin, concentric membrane and/or thick slough covered the distal half and occasionally the entire esophagus. This layer, yellow or blackened, could be peeled away to reveal underlying friable esophageal submucosa. The membrane was composed of fibrinous exudate and inflammatory cells; there was no basement membrane, hence the term pseudomembrane. Patients were treated with histamine H2 receptor antagonists or proton pump inhibitors for about 3 months and followed by endoscopy or clinical observation. All became asymptomatic; the pseudomembrane had disappeared in 32 who underwent follow-up endoscopy. It recurred in 3 of 38 being followed (mean 3.2 years), again associated with another illness requiring hospitalization. The long-term outcome was poor, determined by age and general condition and independent of pseudomembranous esophagitis. Seven patients died within 3 months and 17 during follow-up (mean 42 months, range 5-140 months). Conclusion: Pseudomembranous esophagitis is an unusual condition of unknown cause, probably under-reported and associated with systemic illness. It heals rapidly and recurrence is uncommon. (Gastrointest Endosc 2001;54:730-5.)