January, 1994, through January, 1995, eighteen patients (17 men; median age: 59.9, range: 32-73) with biopsy-proved squamous cell carcinoma (n = 15), adenocarcinoma (n = 2) or undifferentiated carcinoma (n = 1) of the esophagus were treated with concurrent chemo-radiotherapy. All patients had inoperable lesions for unresectable disease (11 patients) or concomitant illness (7 patients); median Karnofsky score was 70 (range: 60-80). According to the 1988 American Joint Committee on Cancer Staging system, one patient was graded as Stage IIA (T2N0 + oropharyngeal cancer T4N1), two Stage IIB (T2N1), twelve Stage III (8 T3N1, 1 T4N0, 3 T4N1) and three Stage IV (2 T3N0M1, 1 T4N0M1). Treatment consisted of two courses of chemotherapy by cisplatin (75 mg/m2 i.v. on days 1 and 29) and 5-FU (1000 mg/m2/24 hours by continuous infusion from days 1 to 4 and from days 29 to 32) along with one course of concomitant radiotherapy at 45 Gy (1.8 Gy per fraction, one fraction per day and 5 fractions a week). After 15-30 days, the patients were treated with a boost dose of 7 Gy by high-dose-rate intraluminal brachytherapy. All patients are assessable for toxicity and seventeen for response. The combined treatment was generally well tolerated, with only one case of WHO grade III toxicity (thrombocytopenia). Eight of the eighteen patients had a complete response (47%); four a partial response (24%); four a minimal response (24%) and one showed stable disease (5%). Only one patient developed local progression, and four distant metastases. All the eight patients with CR are alive without local recurrence (two distant metastases) with a mean follow-up of 6 months. This treatment regimen provides good local tumor resolution with no major toxicity. The value of this study protocol will be determined by the rate of long-term survivors.