Background: Barrett's esophagus is characterized by the presence of specialized columnar epithelium (SCE) in the distal esophagus and is a precursor for dysplasia and adenocarcinoma. Methylene blue is used to selectively stain this type of epithelium within the columnar lined distal esophagus (CLE). The goal of our prospective study was to investigate the staining pattern with methylene blue in patients with visible CLE and a control group with macroscopically normal gastroesophageal junction. Methods: Chromoendoscopy of the distal esophagus with 1% methylene blue was performed on a total of 73 patients (51 with visible CLE, 22 normal control subjects). Biopsies were targeted toward stained or macroscopically abnormal mucosal areas. Unstained CLE was sampled by obtaining 4-quadrant biopsy specimens at 2 cm intervals. Results: The targeted biopsy of stained areas provided histologic proof of SCE with a sensitivity of 98% and a specificity of 61%. The detection of SCE increased with this method in patients with visible CLE (75%), but SCE was also prevalent in the control group (73%). Areas that by their appearance raised a suspicion for dysplasia and adenocarcinoma were already endoscopically apparent in 3 of 4 cases before methylene blue staining and showed different staining patterns. Conclusions: Methylene blue staining increases the rate of detection of SCE, both in patients with visible CLE and with normal gastroesophageal junction. For detection of dysplastic or malignant areas it is important to look for visible mucosal changes. (Gastrointest Endosc 2001;53:47-52.)