Potential modalities for the ablation of Barrett's mucosa are increasing with new technologies. Three of the newest are high- and low-pressure spray cryotherapy and ultrasonic epithelial ablation. Data regarding low-pressure spray cryotherapy are particularly promising. It has a depth of ablation approximating 2 mm, is technically easy to perform, and involves unique cellular mechanisms of injury relative to other thermal techniques that may prove ideally suited for the treatment of GI neoplasms and premalignant lesions such as Barrett's esophagus. A Barrett's ablation trial with cryotherapy is ongoing at the National Naval Medical Center.