The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett's esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett's esophagus were subdivided according to the length of Barrett's mucosa: short-segment Barrett's (<3 cm) and extended Barrett's (> or =3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett's mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett's and 37 (15%) had extended Barrett's esophagus. Patients with short-segment Barrett's esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett's esophagus had increased esophageal acid exposure as did 100% of those with extended Barrett's esophagus. All lengths of Barrett's mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett's esophagus had dysplasia. The length of Barrett's mucosa was > or =3 cm in 25% (4 of 16) of patients with early Barrett's adenocarcinoma. Short-segment Barrett's esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.