Sixteen patients with advanced or recurrent squamous cell carcinoma of the esophagus were treated with cisplatin 80 mg/m2 i.v. on day 1, methotrexate 40 mg/m2 i.v. on day 2 and peplomycin 15 mg/day 24 hours continuous subcutaneous infusion from day 2 to day 5. Each course was repeated every 3 weeks. The overall response rate was 56% (9/16) with no complete response. Of 10 patients with no prior therapy, 7 (70%) showed partial response. Toxic effects were acceptable with no fatalities, but severe nausea and vomiting (56%), transient nephrotoxicity (44%), anemia (44%), thrombocytopenia (31%) and leukocytopenia (19%) occurred. No clinical evidence of pulmonary toxicity was seen. The dose-limiting toxic effect of this regimen was myelosuppression.