Seventeen patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (IFOS) 1.5 mg/m2/day intravenously on days 1-5 every 28 days. Mesna was given concurrently at 20% of the IFOS dose prior to and 4 and 8 h after IFOS for uroprotection. Toxicity in this trial was severe since life-threatening leukopenia occurred in one patient, Grade 3 nausea and vomiting (necessitating termination of treatment) in two patients, and Grade 3 neurotoxicity (cerebellar dysfunction) in two patients. Two patients developed severe infections (Grade 3). Only four patients experienced no toxicity. One patient had a partial response with a response duration of 8 weeks. The median survival of all patients is 10 weeks. It is concluded that IFOS as given in this trial has limited activity in esophagus carcinoma with severe toxicity.