Systemic chemotherapeutic agents, given either singly or in combination, have not affected the dismal prognosis of patients with metastatic or locoregional unresectable carcinoma of the esophagus. New active agents are needed to improve the outcome for these patients. A phase II study evaluated paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour intravenous infusion with granulocyte colony-stimulating factor support to patients with unresectable locoregional or metastatic carcinoma of the esophagus. Response rate, duration of response, and toxicity were assessed. No prior chemotherapy or biologic therapy was allowed, but radiotherapy to a limited field that did not compromise signal lesion evaluation could have been given. The starting paclitaxel dose was 250 mg/m2 repeated every 21 days. The study group included 44 men and seven women with a median age of 57 years and a median Zubrod performance status of I. Among 51 evaluable patients, one complete response and 15 partial responses (PRs) occurred, for a total response rate of 31%. In addition, 11 (22%) achieved a minor response. Among 33 patients with adenocarcinoma, 12 achieved either a complete response (one patient) or a PR (11 patients), and six patients had a minor response. Four of 18 patients with squamous cell carcinoma had a PR and five (28%) had a minor response. The median duration of PR was 17 weeks (range, 7 to 58 weeks). At a median follow-up of 12+ months, 28 patients are alive, with an actuarial median survival duration of 10.2 months (range, 2 to 20+ months). Paclitaxel was well tolerated. Granulocytopenia was frequent, resulting in 11 hospitalizations in nine patients. Grade 3 neuropathy was observed in three patients. Our data suggest that paclitaxel is active against both adenocarcinoma and squamous cell carcinoma of the esophagus. Plans to study paclitaxel in combination with cisplatin and 5-fluorouracil in this group of patients are under way.