This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barrett's esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 +/- 0.2 mm), nondysplastic Barrett's (2.6 +/- 0.2 mm), and Barrett's with dysplasia (2.9 +/- 0.3 mm) were similar. With staining, Barrett's mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barrett's were 68% and 85%, respectively. Barrett's with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barrett's (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.