Between January 1981 and December 1986, 20 patients with adenocarcinoma of the esophagus and gastroesophageal junction were entered into a prospective study involving combined radiation therapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin) as primary management. Nine patients with Stage I or II disease received definitive treatment consisting of 6000 cGy in 6 to 7 weeks and 5-FU (1000 mg/m2/24 hours) as a continuous intravenous (IV) infusion for 96 hours starting on days 2 and 29. Mitomycin (10 mg/m2) was administered as a bolus injection on day 2. Ten patients with extraesophageal and disseminated disease (Stages III and IV) and one patient with an unresectable anastomotic recurrence were considered palliative. Generally the palliative regimen did not differ from the definitive except for the radiation dose which in seven of the 11 patients was less than 6000 cGy (4000-5600 cGy). The range of follow-up was 6 to 74 months and no patient was lost to follow-up. Seven of the eight evaluable definitively treated patients were complete responders. The median relapse-free survival was 10 months and the median survival was 15 months in this group. In the palliative group, six of nine evaluable patients had relief of dysphagia until death or last follow-up with a median duration of 8 months. Our results indicate that combined modality treatment with infusional 5-FU, mitomycin, and radiation is an effective and well-tolerated treatment for adenocarcinoma of the esophagus and gastroesophageal junction. This treatment regimen offers palliation and some chance for cure to those patients who are inoperable, unresectable, or who refuse surgery.