OBJECTIVE To evaluate the response rate and impact on quality of life of vinorelbine given as cycles of 30 mg/m(2) weekly for 6 weeks to patients with malignant pleural mesothelioma. METHODS Twenty-nine patients with histologically proven malignant pleural mesothelioma were enrolled (26 male patients and three female patients; median age, 58 years [range, 29 to 77 years]). Seventeen patients had epithelioid tumors, two had sarcomatoid tumors, and 10 had biphasic tumors. The International Mesothelioma Interest Group staging system was used: one patient had stage Ib disease, 10 had stage II disease, eight had stage III disease, and 10 had stage IV disease. Patients were treated with weekly injections of vinorelbine 30 mg/m(2). A cycle consisted of six weekly injections. The new guidelines to evaluate the response to treatment in solid tumors were used. Responses were measured by spiral computed tomography scan. RESULTS All twenty-nine patients had measurable disease and were assessed for response. There were seven partial responses (24% [95% confidence interval, 10% to 44%]), 16 patients had stable disease (55%), and six patients had disease progression on therapy (21%). The median number of vinorelbine injections was 12 (range, 2 to 30). Quality-of-life analyses showed a benefit for vinorelbine therapy. CONCLUSIONS Vinorelbine shows promise in the palliation of patients with malignant pleural mesothelioma. The relatively low toxicity of the drug suggests that trials of vinorelbine in combination with other agents should be feasible.