Thirty-five non-pretreated patients (29 male, six female) with malignant pleural mesothelioma, median age of 68.5 years (range, 29 to 78 years) and a median performance status of 80% (range, 60% to 100%) were treated with 70 mg/m2 Pirarubicin. The treatment was repeated every 3 to 4 weeks (median duration per cycle, 23 days) up to progression or severe toxicity. The median cumulative dose given was 294 mg/m2, or 4.5 cycles. All patients were evaluable regarding response. Three partial remissions were achieved, leading to a remission rate of 8.6%. The median duration of remission was 6 months. Five patients achieved minor response, and a further 14 patients were stable under treatment with Pirarubicin. The median survival time was 10.5 months. Leukocytopenia was the main dose-limiting factor and 20% of the patients experienced World Health Organization (WHO) Grades III and IV. Anemia and thrombocytopenia were mild. Nausea and vomiting, WHO Grades I and II, were observed in 46% of all patients. Alopecia, Grades I and II, was seen in 47% and Grade III in 6%. No signs of cardiac dysfunction were detectable, except for cardiac arrhythmia in four patients (11%). Pirarubicin is an active drug in the treatment of pleural mesothelioma with fewer severe side effects than doxorubicin.