BACKGROUND AND STUDY AIMS: Patients with cancers of the head and neck have a strong tendency to develop early synchronous and metachronous carcinomas of the esophagus. In many of these patients, whose general condition is poor as a result of alcohol and tobacco abuse, the second primary cancers require minimally invasive treatment. The aims of this study were to evaluate the efficacy of photodynamic therapy for the treatment of early esophageal carcinomas and to compare the results obtained with three different photosensitizers (hematoporphyrin derivative), porfimer sodium (Photofrin II), and meta-(tetrahydroxyphenyl)chlorin (m-THPC). PATIENTS AND METHODS: Thirty-one early squamous cell carcinomas (Tis or T1a) of the esophagus were treated by photodynamic therapy in 24 patients. Nine tumors were treated with hematoporphyrin derivative, eight with Photofrin II and 14 with m-THPC. RESULTS: The early cancers were cured in 84% of patients after a mean follow-up period of 2 years. Because the number of cases included in each group was small, the differences in recurrence rates for the different photosensitizers could not be evaluated statistically, but m-THPC was more phototoxic, induced a shorter period of photosensitization of the skin, and had better selectivity than either of the other photosensitizers. There were four major complications: two stenoses and two esophagotracheal fistulas. CONCLUSIONS: Photodynamic therapy eradicates early squamous cell carcinomas (Tis and T1a) of the esophagus efficiently. Transmural necroses leading to fistulas can be avoided by using a low-penetrating wavelength of laser light (green light at 514.5 m instead of red light at 630 or 652 nm). Stenoses always result from circumferential irradiation of the esophageal wall, and this can be avoided by using a 180 degrees or 240 degrees windowed cylindrical light distributor