Platinum-based combination chemotherapy regimens increasingly are accepted as a first-line treatment option for patients with advanced gastroesophageal adenocarcinoma. While active, such regimens also have been associated with toxicity. Vinorelbine is both well tolerated and active in patients with advanced breast, lung cancer, and squamous cell carcinoma of the esophagus, but has not previously been evaluated as a single agent in gastroesophageal adenocarcinoma. We, therefore, performed a Phase II study to assess the activity of vinorelbine in this disease. Twenty-nine patients with previously treated or untreated metastatic gastroesophageal adenocarcinoma were treated with weekly vinorelbine, administered at a dose of 25 mg/m2, and were followed for evidence of radiologic response, toxicity, and survival. Patients received a median of 8 weeks of therapy. While mild myelosuppression was common, only 17 percent of the treated patients developed Grade 3 or Grade 4 neutropenia. Other toxicities included Grade 1-2 constipation in 31 percent, and Grade 1-2 neuropathy in 13 percent of patients. The overall radiologic response rate was 7 percent, the median progression-free survival time was 1.9 months and the median overall survival time was 7.8 months. We conclude that vinorelbine has minimal toxicity but only minor antitumor activity in patients with advanced gastroesophageal adenocarcinoma.