This Eastern Cooperative Oncology Group phase II trial was conducted to study the effectiveness of docetaxel in patients with malignant mesothelioma. Patients were treated with docetaxel 100 mg/m2intravenously administered as a 1-hour infusion repeated every 3 weeks. The study accrued a total of 20 patients, 1 of whom was considered ineligible. Of the 19 eligible patients, 1 patient (5%) achieved a partial response, 3 patients (16%) had stable disease, 11 patients (58%) had progressive disease, and 4 patients (21%) were unevaluable. The study was terminated after the first accrual stage because of an insufficient number of complete or partial responses. To date, only 1 patient (with stable disease) has not relapsed. The estimated median survival time is 4 months and the estimated median time to treatment failure is 2.2 months. There were 3 early deaths associated with the treatment regimen: severe gastrointestinal toxicity, hemorrhage, and an acute pulmonary event. Docetaxel as a single agent does not demonstrate evidence of activity in malignant mesothelioma.