Cytomegalovirus (CMV) esophagitis is an important cause of esophageal ulceration in patients with the acquired immunodeficiency syndrome. However, the endoscopic appearance of these lesions has not been well characterized. During a 3-year period, we identified 141 CMV esophageal ulcerations endoscopically in 33 patients. CMV esophagitis was the index diagnosis of human immunodeficiency virus (HIV) infection in 8 patients. Odynophagia was almost uniformly present, although gastrointestinal bleeding was the initial manifestation in 5 patients. Multiple ulcers were identified in 58% of patients. Giant ulcers were seen in 28%, whereas 43% of the lesions were less than 1 cm in greatest dimension. The majority of the lesions were located in the middle to distal section of the esophagus. The ulcers were characterized as either shallow or of intermediate depth in 74% of patients; deep ulcers were seen in 8%; diffuse erosive disease was found in 6%; and the ulcers had a "heaped up" appearance in 12%. In contrast to reports from previous studies, CMV esophageal disease appeared highly variable endoscopically. Multiple, well-circumscribed ulcerations were the most common endoscopic findings, although lesions could vary in number, size, and appearance. As this lack of uniformity may cause CMV esophagitis to be confused with other conditions characterized by esophageal ulceration, all HIV-infected patients with esophageal ulceration should undergo endoscopy with biopsy so that a definitive diagnosis can be obtained.