Twelve patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy. Five patients also had early, superficial esophageal cancers and five had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Patients were maintained on omeprazole and followed for 6-54 months. In patients with Barrett's esophagus, photodynamic therapy ablated dysplastic mucosa and malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barrett's mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in three patients. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5-7 days. In four patients with extensive circumferential mucosal ablation in the mid or proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.