Paclitaxel is an active agent for adenocarcinomas and squamous cell carcinomas of the esophagus and is a radiation sensitizer. We sought to investigate the toxicity and complete response rate of paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Forty-one patients with esophageal cancer were studied, 29 with adenocarcinomas and 12 with squamous cell cancers. Twelve patients had tumor extension into the proximal stomach and/or abdominal adenopathy. Patients received paclitaxel 60 mg/m2 by 3-hour intravenous (i.v.) infusion, and cisplatin 25 mg/m2 weekly on days 1, 8, 15, and 22. Radiation was administered concurrently to a total dose of 39.60 Gy, in 1.80 Gy fractions, for 22 treatments. Patients with medical or surgical contraindications to esophagectomy received 2 additional weeks of paclitaxel with a radiation boost to 50.4 Gy. Neutropenia was the most common grade 3/4 toxicity occurring in 10 patients (24%). Only 2 patients (5%) had grade 4 esophagitis requiring parenteral nutrition. Twelve patients (29%) obtained a complete response. The 2-year progression-free and overall survival rates were 40% and 42%, respectively. Esophagitis was less severe than expected and prophylactic enteral feeding tubes were not necessary. Additional effective systemic treatments are needed to reduce the development of distant metastases.