The aim of this study was to appreciate the tolerance and efficacy of a new nonoperative therapy for inoperable esophageal squamous cell carcinoma based on chemotherapy (5FU-cisplatinum) and concomitant splitcourse radiation therapy. Twenty five symptomatic patients (24 males, 1 female, mean age: 59 yrs, range: 41-72 yrs) were included. Five had 2 esophageal carcinoma, 5 an associated upper respiratory tract tumor and 2, relapse after surgery. Nine patients had a tumor limited to the esophagus (stage I or II) but were considered at high surgical risk. Sixteen had stage III disease with mediastinal involvement in 13 cases, nodal involvement in 4 and distant metastasis in 7. Treatment consisted of 2 cycles of chemotherapy with 5-FU (1 g/m2/24 h by continuous infusion for 5 days, D1-D5 and D29-D33) and cisplatinum (70 mg/m2 IV bolus on D2 and D30). Radiation therapy was concomitant in 2 courses delivering 20 grays in 5 days (D1-D5 and D29-D33). On the first day of the treatment, peroral endoscopic dilation or Nd-YAG laser therapy was applied. At the end of treatment all the patients could eat. Histoendoscopic control was performed 8 weeks after the beginning of therapy. Seventeen of the 24 patients had a complete response with negative biopsies. Of the 7 patients with metastatic disease, only 4 were evaluable for response to chemotherapy: one with hepatic metastasis had a complete response for 12 months, 2 had stable disease and one progressive disease.(ABSTRACT TRUNCATED AT 250 WORDS)