Cisplatin-containing regimens are active in the treatment of esophageal cancer, with response rates of 25% to 35% in advanced disease. Carboplatin is less toxic than cisplatin; as a single agent, several responses were seen against esophageal tumors. To better define the role of carboplatin in esophageal cancer, the authors treated 19 chemotherapy-naive patients with advanced squamous cell carcinoma of the esophagus with carboplatin and vinblastine. Carboplatin (450 mg/m2 intravenously [IV] on days 1, 29, 57, and every 6 weeks thereafter) was given with vinblastine (5 mg/m2 IV on day 1 and then every 2 weeks). No major responses were seen. No significant renal toxicity and only mild gastrointestinal toxicity (emesis, diarrhea) were observed. Hematologic toxicity was more severe in patients with prior radiation therapy (RT), with three of six patients with prior RT exhibiting Grade 4 hematologic toxicity. Although generally less toxic than cisplatin-containing regimens, carboplatin and vinblastine is also less active in the treatment of squamous cell carcinoma of the esophagus. Hematologic toxicity with this regimen was severe in patients who had received prior RT.