Eleven patients with high-grade mucosal dysplasia in a columnar-lined oesophagus and 2 patients with a squamous carcinoma (uT1) underwent photodynamic therapy (PDT) and argon-plasma coagulation (APC). For PDT, 5-aminolevulinic acid (5-ALA) was given orally (60 mg/kg) and treated endoscopically with a light dose of 150 J/cm2 (100 mW/cm2) at 635 nm 4-6 h later. A second PDT was performed under the same conditions 2-3 weeks later. Patients who received APC were treated 4 times on average to reach radical Barrett mucosa eradication. All patients were consistently given medication to suppress acid production. No complications occurred in either group. Follow-up endoscopies and multiple biopsies for 3-42 months showed squamous regeneration in the dysplastic columnar-lined oesophagus in all 11 patients. Two patients with squamous carcinoma were found to have a recurrence 9 and 12 months later. PDT with 5-ALA-induced endogenous prophyrins, as well as APC combined with omeprazole protection, can eradicate superficial high-grade dysplastic mucosa in Barrett's oesophagus. However, we did not succeed in destroying a manifest carcinoma.