Advanced squamous cell carcinoma of the head and neck, lung, esophagus, and uterine cervix is still a challenging cancer to the medical practice. We have treated 23 such patients with a combination of cis-platinum, vincristine, and peplomycin. Cis-platinum was given at a dose of 60 mg/m2 on day 1, and 1.0 mg/m2 of vincristine was given on day 3, followed 6 hours later by peplomycin 10 mg/day by continuous infusion iv or sc over the next 5 days. This combination was given every 3 weeks. The overall response rate was 71% for 17 evaluable patients, including one complete response. The median duration of response and survival was 2 and 5 months, respectively. Six other patients with esophageal and cervical carcinoma were treated with two cycles of this combination followed by radical radiation therapy or surgery. Five of them achieved significant response prior to radical treatment. Major side effects were nausea, vomiting, alopecia, and mild myelotoxicity, which were acceptable. This regimen, with a high response rate and acceptable toxicity, warrants further investigation.