In order to find an effective and suitable chemotherapy regimen for preoperative treatment of esophageal cancer, patients with inoperable or metastatic disease were treated with a combination of etoposide and cisplatin. Of 27 evaluable patients, 13 had squamous cell carcinoma, 13 adenocarcinoma, and 1 muco-epidermoid carcinoma. No complete responses were noted. Nine of 13 patients with squamous cell carcinoma and only one of 13 with adenocarcinoma showed a partial response. Nine of 10 responders achieved a partial response after 2 courses, one after 4 courses. There was one toxic death, due to sepsis during leukopenia. Other toxicities were alopecia, nausea and vomiting, nephrotoxicity, thrombocytopenia and leukopenia.