Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was predominantly myelosuppression with a median WBC nadir of 1.8 cells/ul. Seven patients required hospitalization for nadir sepsis. Ifosfamide has minimal activity in esophageal cancer and causes severe myelosuppression.